The acute host response to Clostridium difficile is
initiated by toxin-mediated damage, loss of epithelial integrity and the
detection of translocating bacteria. Intestinal epithelial cells and resident
innate immune cells secrete pro-inflammatory chemokines (such as chemokine C-X-C
motif ligand 1 (CXCL1), CXCL2, and interleukin-8 (IL-8)) and pro-inflammatory
cytokines (such as IL-1β, IL-12 and IL-23), which leads to the
recruitment of neutrophils and the activation of innate lymphoid cells (ILCs).
IL-12 signalling drives the expression of interferon-γ (IFNγ),
whereas IL-1β and IL-23 signalling induces the production of IL-22. The
effector cytokines IFNγ and IL-22 induce defence mechanisms such as
increased phagocytic activity of macrophages and neutrophils and the production
of antimicrobial peptides and enzymes that synthesize reactive oxygen species
(ROS) and reactive nitrogen species (RNS). These defence mechanisms limit
bacterial dissemination, attenuate toxin activity and repair epithelial damage.
DCs, dendritic cells.