The gut microbiota is associated with clearance of Clostridium difficile infection independent of adaptive immunity

AbstractClostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium is the leading single cause of nosocomial infections in the United States. A major risk factor for C. difficile infection (CDI) is prior exposure to antibiotics as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80-90% success rate of fecal microbial transplants in treating recurrent infection. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, Random Forest analysis using only 2 members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.ImportanceC. difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens as inherent differences in the baseline community structure of animals may bias findings.

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The Gut Microbiota Is Associated with Clearance ofClostridium difficileInfection Independent of Adaptive Immunity

mSphere ◽

10.1128/mspheredirect.00698-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 11

Author(s):

Jhansi L. Leslie ◽

Kimberly C. Vendrov ◽

Matthew L. Jenior ◽

Vincent B. Young

Keyword(s):

United States ◽

Immune Response ◽

Clostridium Difficile ◽

Gut Microbiota ◽

Adaptive Immunity ◽

Adaptive Immune Response ◽

The United States ◽

Content Type ◽

Adaptive Immune

ABSTRACTClostridium(Clostridioides)difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor forClostridium difficileinfection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance ofC. difficilehas yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance ofC. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance ofC. difficilefrom the murine gastrointestinal tract.IMPORTANCEClostridium difficileinfection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels ofC. difficilecolonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance ofC. difficilefrom the GI tract. Our results show that clearance ofC. difficilecan occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.

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Long-term and short-term immunity to SARS-CoV-2: why it matters

Microbiology Australia ◽

10.1071/ma21010 ◽

2021 ◽

Vol 42 (1) ◽

pp. 34

Author(s):

John Zaunders ◽

Chansavath Phetsouphanh

Keyword(s):

Immune Response ◽

Adaptive Immunity ◽

Viral Infections ◽

Adaptive Immune Response ◽

Recurrent Infection ◽

Adaptive Immune System ◽

Upper Respiratory Tract ◽

Short Term ◽

Adaptive Immune ◽

Tract Infections

The adaptive immune system, regulated by CD4 T cells, is essential for control of many viral infections. Endemic coronavirus infections generally occur as short-term upper respiratory tract infections which in many cases appear to be cleared before adaptive immunity is fully involved, since adaptive immunity takes approximately 1.5–2 weeks to ramp up the response to a primary infection, or approximately 1 week for a recurrent infection. However, the adaptive immune response to SARS-CoV-2 infection will be critical to full recovery with minimal long-lasting effects, and to either prevention of recurrence of infection or at least reduced severity of symptoms. The detailed kinetics of this infection versus the dynamics of the immune response, including in vaccinated individuals, will largely determine these outcomes.

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Adaptive Immunity: The Role of Toll-Like Receptors

Austin Journal of Allergy ◽

10.26420/austinjallergy.2021.1038 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yamaguchi R ◽

◽

Sakamoto A ◽

Yamaguchi R ◽

Haraguchi M ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Autoimmune Diseases ◽

Adaptive Immunity ◽

Th17 Cells ◽

Adaptive Immune Response ◽

Toll Like Receptors ◽

Adaptive Immune ◽

Interleukin 23

The central mediators of the adaptive immune response are T cells. The clonal expansion of T cells required for adaptive immunity results from the innate immune response, which is triggered by the stimulation of Toll-Like Receptors (TLRs). The adaptive immune response can cause autoimmune diseases, and Th17 cells are known to contribute to several autoimmune diseases. Pathogenic Th17 cells are induced by Interleukin 23 (IL-23) and IL-1Β. Resiquimod (a TLR7/8 agonist) significantly enhances IL-23 production by human macrophages, and lipopolysaccharide (a TLR4 agonist) slightly enhances it. Interestingly, IL-23 levels are significantly attenuated after sequential stimulation with lipopolysaccharide and resiquimod, indicating cross-talk between the TLR4 and TLR7/8 signaling pathways. In this review, we discuss the pivotal role of TLRs in triggering innate immunity and inducing adaptive immunity, leading to autoimmune diseases.

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The role of the T-helper/T-suppressor ratio in the adaptive immune response: a dynamical model

Journal of Physics A Mathematical and Theoretical ◽

10.1088/1751-8121/aaed5e ◽

2018 ◽

Vol 51 (50) ◽

pp. 505602 ◽

Cited By ~ 1

Author(s):

A Annibale ◽

L A Dziobek-Garrett ◽

H Tari

Keyword(s):

Immune Response ◽

Adaptive Immune Response ◽

Dynamical Model ◽

T Helper ◽

Adaptive Immune

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The Pathogenic Role of the Adaptive Immune Response to Modified LDL in Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2012.00076 ◽

2012 ◽

Vol 3 ◽

Cited By ~ 8

Author(s):

Gabriel Virella ◽

Maria F. Lopes-Virella

Keyword(s):

Immune Response ◽

Adaptive Immune Response ◽

Pathogenic Role ◽

Adaptive Immune ◽

Modified Ldl

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Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Frontiers in Immunology ◽

10.3389/fimmu.2021.652252 ◽

2021 ◽

Vol 12 ◽

Author(s):

Carlos A. Labarrere ◽

Ghassan S. Kassab

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Global Economy ◽

Rna Viruses ◽

Severe Disease ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Recognition Protein ◽

Pattern Recognition Protein

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

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Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.050103 ◽

2010 ◽

pp. 224-234

Author(s):

Paul Klenerman

Keyword(s):

Infectious Disease ◽

Immune Response ◽

Pattern Recognition ◽

Adaptive Immunity ◽

Adaptive Response ◽

Critical Role ◽

Adaptive Immune Response ◽

Structural Features ◽

Adaptive Immune ◽

Single Organism

Following the innate immune response, which acts very rapidly, the adaptive immune response plays a critical role in host defence against infectious disease. Unlike the innate response, which is triggered by pattern recognition of pathogens, i.e. features that are common to many bacteria or viruses, the adaptive response is triggered by structural features—known as antigens or epitopes—that are typically unique to a single organism....

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Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0040 ◽

2020 ◽

pp. 325-336

Author(s):

Paul Klenerman

Keyword(s):

Immune Response ◽

Immune Responses ◽

Adaptive Immunity ◽

Innate Immune Response ◽

Molecular Basis ◽

Adaptive Immune Response ◽

Antigenic Specificity ◽

Adaptive Immune Responses ◽

Research Attention ◽

Adaptive Immune

The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.

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