Host Immune Responses to Surface S-Layer Proteins (SLPs) of Clostridioides difficile

Abstract

Clostridioides difficile, a nosocomial pathogen, is an emerging gut pathobiont causing antibiotic-associated diarrhea. C. difficile infection involves gut colonization and disruption of the gut epithelial barrier, leading to the induction of inflammatory/immune responses. The expression of two major exotoxins, TcdA and TcdB is the major cause of C. difficile pathogenicity. Attachment of bacterial abundant cell wall proteins or surface S-layer proteins (SLPs) such as SlpA with host epithelial cells is critical for virulence. In addition to being toxins, these surface components have been shown to be highly immunogenic. Recent studies indicate that C. difficile SLPs play important roles in the adhesion of the bacteria to the intestinal epithelial cells, disruption of tight junctions, and modulation of the immune response of the host cells. These proteins might serve as new targets for vaccines and new therapeutic agents. This review summarizes our current understanding of the immunological role of SLPs in inducing host immunity and their use in the development of vaccines and novel therapeutics to combat C. difficile infection.

Keywords: S-layer proteins; antibiotic-associated diarrhea; cell wall proteins; therapeutics; vaccine.

Figure 1

The SLPs of C. difficile mediate the adhesion and activation of the immune cells. Nascent SlpA peptide is cleaved by the protease Cwp84 into the LMW and HMW subunit, which forms the mature SlpA complex of the SLP layer of the cell wall [31,32,33]. SLPs mediate adhesion via TLR4 and disrupt the tight junction of the intestinal epithelial cells and further activate dendritic cells/macrophages, which in turn produce various cytokines and chemokines leading to the induction of Th1/Th2 and humoral response [9,27]. Interleukin (IL), Dendritic cells (DC), Low molecular weight (LMW), High molecular weight (HMW), Toll-like receptor 4 (TLR4).