Author Correspondence author
Molecular Microbiology Research, 2024, Vol. 14, No. 1 doi: 10.5376/mmr.2024.14.0001
Received: 11 Nov., 2023 Accepted: 16 Dec., 2023 Published: 01 Jan., 2024
Chen C., 2024, Interaction between pathogenic mechanism of Salmonella and host immune system, Molecular Microbiology Research, 14(1): 1-9 (doi: 10.5376/mmr.2024.14.0001)
Salmonella is a gram-negative bacterium widely distributed in nature, mainly existing in the intestines and environment of animals. It can cause human infection through eating contaminated food or drinking water, contact with infected animals or their feces, etc. The symptoms of Salmonella infection include diarrhea, fever, abdominal pain, nausea, vomiting, etc. In severe cases, it may also cause serious complications such as sepsis, organ damage, and pneumonia. Globally, millions of people are infected with Salmonella every year, and tens of thousands of people die, seriously affecting human health and life safety (Avondt et al., 2015).
The molecular mechanism of Salmonella infection and the interaction with the host immune system is one of the hot topics in recent years. The virulence factors of Salmonella mainly include serotonin, endotoxin, flagella, etc. Among them, serotonin is a molecule that can cause intestinal inflammation, which can promote Salmonella invasion into host cells and inhibit the inflammatory response of the host immune system. Endotoxin is a molecule that causes inflammatory responses, which can activate the inflammatory response of the host immune system, but also cause damage to host tissues. Flagella is a locomotive organ of Salmonella that can help Salmonella evade the attack of the host immune system. In addition, Salmonella can produce various molecules, such as surface proteins, lipopolysaccharides, etc., to activate the inflammatory response of the host immune system and form inflammatory foci. At the same time, Salmonella infection can also cause immune evasion of the host immune system. Salmonella can evade the surveillance and attack of the host immune system by interfering with the signal transduction pathway of host cells. In addition, Salmonella infection can also affect the cellular and humoral immunity of the host immune system. It has been found that after Salmonella infection, the functions of macrophages and dendritic cells in the host immune system are inhibited, and the activation and proliferation of T cells are also inhibited, thus reducing the resistance of the host immune system (Jantsch et al., 2011).
In terms of the diagnosis and treatment of Salmonella infection, there are currently multiple methods and means available. For example, bacterial culture, molecular biology detection, and antibiotic treatment. Among them, bacterial culture is currently the most commonly used method, but it has a higher time and cost, and there is a certain rate of misdiagnosis. Molecular biology detection can rapidly and accurately detect the presence of Salmonella, but it requires more professional experimental conditions and equipment. Antibiotic treatment is one of the conventional methods for Salmonella infection, but due to the abuse and improper use of antibiotics, there have been multiple drug-resistant Salmonella strains, which bring certain challenges and difficulties to treatment. Therefore, in-depth research on the molecular mechanism of Salmonella pathogenesis and the interaction with the host immune system, exploring the pathophysiological process and treatment methods of Salmonella infection, is one of the important directions of medical research today. I believe that with continuous exploration and efforts, there will be more breakthroughs in the future, providing more scientific and effective methods and means for the prevention and treatment of Salmonella infection.
1 Basic Characteristics of Salmonella
1.1 The traditional liquor brewing process and its characteristics
Salmonella is a gram-negative bacterium and a common enteropathogen. Based on the analysis of 16S rRNA sequences, Salmonella can be divided into two subgenera: Salmonella subgenus and Citrobacter subgenus (Denise et al., 2004). Among them, the Salmonella subgenus includes common Salmonella strains, with more than 2 500 different serotypes. They share common pathogenicity and can cause different symptoms ranging from mild diarrhea to severe sepsis. The Citrobacter subgenus includes some enteric bacteria related to Salmonella, such as Paratyphi and Lactobacillus acidophilus (Denise et al., 2004).
The morphological structure of Salmonella is similar to that of other gram-negative bacteria, with cells that are short rods with a size of approximately 0.7~1.5 micrometers × 2~5 micrometers. It has various virulence factors such as collagenase and lipopolysaccharide. Salmonella has flagella and a capsule on its surface, and the flagella can help it locate on the intestinal mucosa and invade host cells. The capsule can help Salmonella defend against the attack of the host immune system and enhance its pathogenicity. Salmonella colonies are grayish white or light yellow, with a smooth surface and neat edges, and sometimes secrete mucus (Figure 1). Salmonella is widely distributed in nature, mainly found in the intestines of animals and the environment, such as water, soil, plants, and food (Denise et al., 2004). Salmonella can cause human infections through eating contaminated food or drinking water, or contact with infected animals or their feces. The high-risk population for Salmonella infection includes young children, the elderly, and immunocompromised individuals. Globally, millions of people are infected with Salmonella each year, and tens of thousands die, seriously affecting human health and life safety. Therefore, preventing and controlling Salmonella infections is of great significance.
Figure 1 Salmonella electron microscopic image (Salmonella Testing Technique, 2021) |
1.2 The growth characteristics and metabolic pathways of Salmonella
The growth characteristics and metabolic pathways of Salmonella have many similarities with other bacteria. Salmonella is an obligate anaerobe that can grow under low oxygen or anaerobic conditions. It can grow on various culture media, such as ordinary nutrient agar culture media and Escherichia coli selective agar culture media. Under suitable temperature and pH conditions, Salmonella can multiply rapidly and form colonies.
Salmonella has a relatively diverse metabolic pathway and can utilize various organic and inorganic substances as carbon sources, nitrogen sources, and energy sources. Salmonella can metabolize various monosaccharides and disaccharides, such as glucose, fructose, lactose, and sucrose. It can also utilize complex organic substances such as fatty acids, amino acids, and peptides for metabolism. Additionally, Salmonella can utilize inorganic substances such as sulfates and nitrites for metabolism. In the metabolic pathway, the oxidative phosphorylation pathway is the main energy source for Salmonella. In this pathway, Salmonella oxidizes substrates to CO2 and H2O, releasing energy through enzymes such as ATP synthase. At the same time, Salmonella can also perform anaerobic respiration to obtain energy by oxidizing inorganic substances such as sulfates and nitrites (Behnsen et al., 2015).
The growth characteristics and metabolic pathways of Salmonella have strong adaptability and diversity. It can utilize various organic and inorganic substances for metabolism, adapting to different environmental conditions and nutritional sources. This also provides a certain basis for Salmonella to survive and spread in the intestines or environment.
1.3 The virulence factors of Salmonella and their mechanism of action
As a Gram-negative bacterium, Salmonella is one of the commensal bacteria in the intestines of humans and animals. Although Salmonella is not harmful to the human body under normal conditions, when they enter and multiply in the human body, they can cause various problems, including food poisoning and intestinal infections.
The pathogenicity of Salmonella is mainly caused by various virulence factors. These virulence factors can help Salmonella invade host cells, disrupt the host immune system, and cause intestinal inflammation, etc. Among them, the surface antigens of Salmonella can help it adhere to the intestines, invade host cells, and evade attacks from the host immune system. The surface antigens of Salmonella include capsules, flagella, O antigens, H antigens, etc. Different combinations of these surface antigens form different strains and serotypes. For example, certain strains of Salmonella can evade attacks from the host immune system by changing the combination of capsules. It can also secrete various toxins, including endotoxins, cytotoxins, and exotoxins. These toxins can destroy the structure and function of host cells, causing cell death and tissue damage. The endotoxin of Salmonella is a lipopolysaccharide that can cause an inflammatory response in the host immune system, leading to symptoms such as vasodilation and hypotension. Its cytotoxin can destroy the membrane structure of host cells, leading to cell death. For example, Salmonella cytolysin is a cytotoxin that can destroy the membrane of host cells. The exotoxin of Salmonella can inhibit the signal transduction pathway of the host immune system and disrupt the immune response of host cells (Behnsen et al., 2015).
Salmonella also has various transport proteins, including Salmonella pathogenicity island (SPI) 1, SPI-2, etc. These transport proteins can help Salmonella enter host cells and evade attacks from the host immune system, thereby causing infections. SPI-1 and SPI-2 are two different transport proteins that play roles in different stages of infection. SPI-1 can help Salmonella enter host intestinal epithelial cells, while SPI-2 can help Salmonella survive and multiply inside host cells.
2 The Process of Salmonella Infection
2.1 The routes and processes of Salmonella infection
Salmonella typically survives and reproduces in the intestines of humans and animals. People can contract Salmonella by consuming contaminated food or drinking contaminated water. In addition, they can also become infected with this bacterium through contact with animals infected with Salmonella, or by directly touching objects contaminated with Salmonella (Figure 2).
Figure 2 Land Bridge ESM Salmonella chromogenic agar (GB 4789.4-2010 Food Microbiology Examination - Salmonella Testing) Note: Salmonella: Purple-red colonies; Non-Salmonella: Blue-green, colorless, or inhibited |
The process of Salmonella infection can be divided into invasion, survival, and reproduction stages. In the invasion stage, Salmonella adheres to and invades host cells through intestinal epithelial cells. Salmonella utilizes structures such as flagella and capsules on its surface to adhere to and invade host cells. Additionally, Salmonella can secrete various toxins, such as Salmonella cytolysin, to disrupt the membrane structure of host cells, promoting cell adhesion and invasion (Sahler et al., 2018) (Figure 2).
In the survival stage, Salmonella needs to evade attacks from the host immune system to survive in the host body. To achieve this, Salmonella can utilize its transport proteins, such as SPI-1, to enter the interior of cells, thereby avoiding attacks from the host immune system. Salmonella also secretes various toxins such as endotoxins and cytotoxins to suppress the immune response of the host immune system and reduce inflammation.
In the reproduction stage, Salmonella utilizes its transport proteins, such as SPI-2, to acquire nutrients from within host cells, allowing it to reproduce and survive. Additionally, Salmonella secretes various enzymes and proteases to disrupt the structure and function of host cells, promoting its growth and reproduction (Hornef et al., 2002). After reproducing inside the cell for a period of time, Salmonella leaves the host cell and further spreads to other host cells or tissues. They escape by disrupting the host cell membrane or are directly phagocytosed by host cells and survive within them.
2.2 The life cycle of Salmonella within the host body
The process of Salmonella within the host body is quite complex. After infecting the host, Salmonella needs to evade the attack of the host immune system to survive within the host. Salmonella adheres to the host cell surface using specific structures such as flagella and pili, and further invades the host cell by releasing virulence factors and secreting systems. Once successfully invading the host cell, Salmonella begins intracellular replication. It utilizes the nutrients and metabolic mechanisms provided by the host cell to synthesize DNA, RNA, and proteins, and continuously replicates itself through the process of division. In this way, Salmonella is able to multiply in large numbers and continue to infect the host.
After reproducing within the cell for a period of time, Salmonella leaves the host cell and further spreads to other host cells or tissues. They can escape by disrupting the host cell membrane or be phagocytosed by host cells and survive within them. Salmonella also employs several strategies to evade surveillance and attack by the host immune system. Through the action of virulence factors, they interfere with the signal transduction pathway of host cells, reducing the resistance of the host immune system. At the same time, Salmonella can also produce various molecules, such as surface proteins and lipopolysaccharides, to activate the inflammatory response of the host immune system, thereby forming inflammatory foci (Sahler et al., 2018).
The survival and reproduction of Salmonella within the host are also influenced by the host immune system. When the host immune system senses the presence of Salmonella, a series of immune responses will be initiated, such as inflammation, phagocytosis by macrophages, etc. Salmonella needs to evade these immune responses in order to survive and multiply within the host. To achieve this, Salmonella can utilize its transport proteins, toxins, etc., to evade attacks by the host immune system.
2.3 The host immune response after Salmonella infection
After Salmonella infection, the host immune system initiates a series of immune responses. The most important of these is the inflammatory response. Inflammation is a protective response of the host immune system that can clear Salmonella and other pathogens, and restore the function of damaged tissues. The characteristics of inflammation include redness, swelling, heat, pain, and tissue damage. During the inflammatory response, the host immune system releases a variety of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 to induce inflammation. The inflammatory response involves vasodilation, increased blood flow, and aggregation of white blood cells to direct immune cells and inflammatory mediators to the site of infection to prevent further spread of the pathogen. In addition, immune cells such as macrophages, dendritic cells, and neutrophils are activated, which eliminate the infection by recognizing and destroying Salmonella, releasing cytotoxins, and producing cytokines.
In addition to the inflammatory response, the host immune system also initiates a macrophage phagocytic response. Macrophages are important immune cells that can phagocytose and kill Salmonella and other pathogens. Macrophages can also release a variety of inflammatory cytokines such as TNF-α, IL-1β, and IL-12 to induce inflammation and promote immune responses.
After Salmonella infection, the host immune system also initiates adaptive immune responses. Adaptive immune responses include cellular immunity and humoral immunity. Cellular immunity mainly clears Salmonella and other pathogens through T cells and macrophages. Humoral immunity mainly clears Salmonella and other pathogens through antibodies. These antibodies can neutralize the virulence factors of Salmonella, prevent its invasion into host cells, and promote its phagocytosis and destruction. In addition, cellular immune responses also play an important role, including cell-mediated immune responses and cytotoxic effects. Activated T cells and natural killer cells release cytotoxins that directly cause the death of infected cells. After successfully fighting Salmonella infection, the immune system forms immunological memory. This means that the host immune system can quickly recognize and respond to reinfection by rapidly activating immune responses to prevent the reproduction and spread of Salmonella.
3 The Interaction of Salmonella with the Host Immune System
3.1 The role of Salmonella in infecting host cells
Before infecting host cells, Salmonella must first adhere to the surface of the host cell. To do this, Salmonella can utilize specific proteins on its surface, such as the FimH protein, to bind to receptors on the surface of the host cell, forming a strong connection. This adhesion allows Salmonella to more effectively invade the host cell interior.
After Salmonella infects the host cell, it enters the interior of the host cell. This process typically relies on Salmonella's type three secretion system (T3SS). The T3SS injects Salmonella proteins directly into the host cell, altering its biological activity. These proteins include those encoded by the pathogenicity island, such as SPI-1 and SPI-2. These proteins help Salmonella evade the attack of the host immune system while also acquiring necessary nutrients and growth conditions within the host cell. In addition to invading the host cell interior, Salmonella can also interact with host cells in other ways. For example, Salmonella can release toxins that disrupt the structure and function of host cells. These toxins include endotoxins, cytotoxins, and hemolysins. These toxins can cause the death of host cells and tissue damage.
3.2 The impact of Salmonella on the host immune system
After Salmonella infection, the host immune system initiates a series of immune responses, such as the inflammatory response and adaptive immune response mentioned earlier. However, Salmonella can also influence the host immune system in various ways to promote its growth and reproduction.
Salmonella first alters the balance of the host immune system. It can release specific molecules that act as inflammatory cytokines and cause inflammation and tissue damage. Additionally, Salmonella can suppress certain components of the host immune system, such as T cells and macrophages, reducing the host's ability to fight the infection. Salmonella also interferes with signal transduction in the host immune system. For example, Salmonella can release proteins such as SipA and SopB through its T3SS to alter signal transduction pathways in host cells. These proteins can interfere with key molecules in cell signaling pathways, such as Rho GTPase, thereby affecting the biological behavior of host cells. Salmonella also exploits the host immune system to promote its own growth and reproduction. For instance, Salmonella can regulate the host immune response by releasing molecules such as flagellin and bile acids. Bile acids are compounds found in bile that are released by Salmonella upon infection. Flagellin stimulates the production of bile acids by host intestinal epithelial cells. Bile acids can interact with the host's TGR5 receptor to inhibit the inflammatory response of immune cells, thereby helping Salmonella evade the host's immune attack (Flynn and Chan, 2003; Raffatellu et al., 2006).
3.3 The immune evasion mechanisms of Salmonella against immune responses
Salmonella can evade the attack of the host immune system through various mechanisms. For example, Salmonella can alter its surface structure to avoid recognition and attack by the host immune system. Salmonella can change the structure of its LPS molecules to evade antibodies and immune cells produced by the host immune system. Salmonella also releases molecules that interfere with the function of the host immune system. These proteins can affect the biological behavior of host cells, making it difficult for them to effectively fight Salmonella infections. Salmonella can also use its T3SS to evade the attack of the host immune system. The T3SS injects Salmonella proteins directly into host cells, altering their biological activity. These proteins can help Salmonella evade the attack of the host immune system while also acquiring necessary nutrients and growth conditions within the host cell (Arciola et al., 2018).
Salmonella can also interfere with the balance of the host immune system. Salmonella can activate the host immune system by releasing specific molecules, such as LPS and flagellin. These molecules stimulate the production of large amounts of inflammatory cytokines, such as TNF-α, IL-1β, IL-6, etc. (Bueno et al., 2007). These inflammatory cytokines cause inflammation and tissue damage, weakening the host's ability to fight the infection and providing a better growth environment for Salmonella.
4 Diagnosis and Treatment of Salmonella Infection
4.1 Diagnostic methods for Salmonella infection
The diagnosis of Salmonella infection is achieved by isolating and identifying Salmonella. Traditional diagnostic methods include cultivation and biochemical analysis. In these methods, samples are usually collected from biological fluids such as blood, feces, urine, etc. of patients. After processing, the samples are cultured and biochemically analyzed to detect the presence of Salmonella. The advantages of these methods are simplicity and ease of operation, but they require a relatively long time and usually take several days to obtain results.
With the development of molecular biology and immunology, modern diagnostic methods have been further improved. For example, PCR technology can rapidly and accurately diagnose Salmonella infection by detecting the genes of Salmonella. Similarly, immunological methods can also detect the level of Salmonella antibodies in patients to determine the presence of Salmonella infection.
In addition to traditional diagnostic methods, there are also new technologies being studied, such as mass spectrometry analysis and fluorescence spectroscopy analysis. The advantages of these methods are fast speed, high sensitivity, good specificity, but they still need further validation and application. Currently, the diagnosis of Salmonella infection is constantly developing and improving. Although traditional diagnostic methods remain important diagnostic tools, the development of modern technology will provide more choices and more efficient methods for the diagnosis of Salmonella infection.
4.2 Treatment methods for Salmonella infection
The treatment methods for Salmonella infection mainly include antibiotic therapy and supportive care. Currently, commonly used antibiotics include fluoroquinolones, cephalosporins, aminoglycosides, and macrolides. These antibiotics can treat Salmonella infection by inhibiting the growth and reproduction of Salmonella. The choice of antibiotics should be based on the drug sensitivity of Salmonella and the clinical condition of the patient (Figure 3). During treatment, adjustments and monitoring should be made based on the patient's condition and adverse drug reactions.
Figure 3 Salmonella detection and culture (GB 4789.4-2010 Food Microbiology Examination - Salmonella Testing) |
Besides antibiotic therapy, supportive care is also an important treatment for Salmonella infection. Supportive care plays an important role in the treatment of Salmonella infection. Salmonella is a type of bacteria that can cause food poisoning or Salmonella infection, usually manifesting as symptoms such as diarrhea, fever, and vomiting. In addition to drug treatment targeting the pathogen, supportive care is one of the key methods to help patients relieve symptoms and promote recovery. Supportive care includes maintaining water and electrolyte balance, correcting malnutrition, and managing symptoms. For example, diarrhea and vomiting can lead to fluid loss and cause dehydration and electrolyte disorder,so providing sufficient fluids and appropriate electrolyte supplements can help maintain balance in the body. Salmonella infection may affect appetite and lead to inadequate nutritional intake. Therefore, providing easily digestible foods and maintaining adequate nutritional intake can help accelerate recovery. Additionally, appropriate medications can help relieve pain and fever, improving patient comfort. During the infection period, proper isolation and rest can help the body fully resist the infection and promote recovery. During treatment, the patient's condition and vital signs should be closely monitored, and complications should be corrected and managed in a timely manner (Wang et al., 2020).
In recent years, some new treatment methods are being studied, such as vaccines and immunotherapy. Vaccines can prevent Salmonella infection by stimulating the immune response of the body. Currently, there are some Salmonella vaccines that have been applied in clinical practice. Immunotherapy can enhance resistance to Salmonella by boosting the immune function of the body. These new treatment methods still need further research and validation.
Although the treatment methods for Salmonella infection are constantly developing and improving, antibiotic therapy and supportive care remain the main treatment methods. With the development of technology and further research, there will be more treatment methods available to provide more options and more efficient methods for the treatment of Salmonella infection.
4.3 The prevention and control of Salmonella infection
Salmonella infection is a common food-borne illness that is mainly transmitted through contaminated food or drinking water. Therefore, the key to preventing Salmonella infection is strengthening food safety management and personal hygiene.
In terms of food safety management, it is necessary to strengthen the supervision of food production and sales to ensure that food meets standards and regulations. Food producers and sellers should follow the corresponding hygiene standards and operating procedures to ensure the hygienic safety of food. Consumers should choose safe and reliable food and pay attention to the preservation and cooking methods of food.
In terms of personal hygiene, attention should be paid to the cultivation of personal hygiene habits. Frequent handwashing should be done to avoid contact with pollutants and pathogens. Hands must be washed before and after handling food, and clean tools and disinfectants should be used to maintain food hygiene. During travel and outdoor activities, hygiene standards and regulations should be followed to avoid drinking contaminated water and eating untreated food.
Vaccination is also an effective means of preventing Salmonella infection. Currently, some Salmonella vaccines have been applied in clinical practice. People at high risk, such as farmers, animal breeders, food processors, etc., should receive the corresponding vaccine to prevent Salmonella infection.
5 Summary and Outlook
This study reviewed the diagnosis, treatment, prevention and control methods of Salmonella infection, and explored their progress and future trends. The aim is to enhance the understanding of Salmonella infection, prevent and control Salmonella infection, and reduce the occurrence and transmission of Salmonella infection. In terms of the diagnosis of Salmonella infection, the study mentioned traditional diagnostic methods and modern diagnostic methods. In traditional methods, culture and biochemical analysis are commonly used methods. Although these methods are simple and easy to perform, they require a long time. Modern diagnostic methods include PCR technology and immunological methods, which can diagnose Salmonella infection quickly and accurately. It is believed that more diagnostic methods will be applied, providing more choices and more efficient methods for the diagnosis of Salmonella infection. In addition, new treatment methods such as vaccines and immunotherapy are being studied.
With the development of technology and the deepening of research, more treatment methods will be applied, providing more choices and more efficient methods for the treatment of Salmonella infection. For the prevention and control of Salmonella infection, it is necessary to strengthen food safety management and personal hygiene habits. In addition, vaccination is also an effective means of preventing Salmonella infection.
As a common disease, Salmonella infection has a significant impact on human health. Therefore, it is necessary to strengthen the understanding of Salmonella infection, prevent and control the occurrence and transmission of Salmonella infection. In the future, research on the mechanism of Salmonella infection, the development and application of Salmonella vaccines, and epidemiological studies on Salmonella infection can effectively prevent and control the occurrence and transmission of Salmonella infection, making greater contributions to human health.
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