The adaptive immune response toClostridioides difficile: A tricky balance between immunoprotection and immunopathogenesis

Abstract

Clostridioides difficile (C. difficile) is the major cause of hospital-acquired gastrointestinal infections in individuals following antibiotics treatment. The pathogenesis of C. difficile infection (CDI) is mediated mainly by the production of toxins that induce tissue damage and host inflammatory responses. While innate immunity is well characterized in human and animal models of CDI, adaptive immune responses remain poorly understood. In this review, the current understanding of adaptive immunity is summarized and its influence on pathogenesis and disease outcome is discussed. The perspectives on what we believe to be the main pending questions and the focus of future research are also provided. There is no doubt that the innate immune response provides a first line of defense to CDI. But, is the adaptive immune response a friend or a foe? Probably it depends on the course of the disease. Adaptive immunity is essential for pathogen eradication, but may also trigger uncontrolled or pathological inflammation. Most of the understanding of the role of T cells is based on findings from experimental models. While they are a very valuable tool for research studies, more studies in human are needed to translate these findings into human disease. Another main challenge is to unravel the role of the different T cell populations on protection or induction of immunopathogenesis.

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs

“…It would be explainable that the increases in cytokines levels may be associated with the colonization of Clostridium_XI. It has been reported that toxins produced by Clostridium_XI triggered circulating immunity to increase the expression of some interleukins, such as IL-1β, prompting immune cells to secrete antimicrobial peptides in an attempt to clear Clostridium_XI from the gut (Hernández Del Pino et al, 2021;Nibbering et al, 2021). This statement coincided with our negative correlation between Clostridium_XI and blood cytokines.…”

Host Immune Responses to Clostridioides difficile: Toxins and Beyond

“…It is important to highlight that with the increasingly complex models, from animal to human studies, it is hard to separate the immune responses to C. difficile from effects mediated by the intestinal microbiome, as the latter has a great influence on both C. difficile colonization and pathogenesis and the intestinal immune responses (Samarkos et al, 2018). The role of the microbiome in the context of FMT has recently been reviewed elaborately (Hernández Del Pino et al, 2021;Littmann et al, 2021). Additionally, other host factors, such as immune suppressive comorbidities and antibiotic treatment, may alter the intestinal immune response even before C. difficile challenges the immune system (Negrut et al, 2020).…”

“…Additionally, other host factors, such as immune suppressive comorbidities and antibiotic treatment, may alter the intestinal immune response even before C. difficile challenges the immune system (Negrut et al, 2020). Considering these aspects, as well the delicate balance between pro-and anti-inflammatory roles for the immune response (Hernández Del Pino et al, 2021), it will be a challenge to generate a complete picture of the role of the immune response in C. difficile colonization and pathogenesis, but we hope that the present review can provide a framework for the interpretation of immunological data from future interventions.…”

Clostridioides difficile toxins enhanced the in vitro production of CXC chemokine ligand 2 and tumor necrosis factor-α via Toll-like receptors in macrophages

“…Recently, key aspects of CDI pathogenesis were reviewed, including the virulence factors that contribute to CDI pathogenesis and the mechanisms whereby TcdA, TcdB, CDT, and other virulence factors trigger inflammation by activating innate immune cells [27]. Macrophages are a major source of inflammatory cytokines in CDI, and their role in aetiology has been noted.…”