Cohabitation in the Intestine: Interactions among Helminth Parasites, Bacterial Microbiota, and Host Immunity

Abstract

Both intestinal helminth parasites and certain bacterial microbiota species have been credited with strong immunomodulatory effects. Recent studies reported that the presence of helminth infection alters the composition of the bacterial intestinal microbiota and, conversely, that the presence and composition of the bacterial microbiota affect helminth colonization and persistence within mammalian hosts. This article reviews recent findings on these reciprocal relationships, in both human populations and mouse models, at the level of potential mechanistic pathways and the implications these bear for immunomodulatory effects on allergic and autoimmune disorders. Understanding the multidirectional complex interactions among intestinal microbes, helminth parasites, and the host immune system allows for a more holistic approach when using probiotics, prebiotics, synbiotics, antibiotics, and anthelmintics, as well as when designing treatments for autoimmune and allergic conditions.

Figure 1. Parallel immunomodulatory strategies of helminths and bacteria in the intestinal tract- mechanisms of Treg induction

Both helminths and several bacterial microbiota species have been credited with host immunomodulatory capabilities, including the induction of Tregs. Various human and mouse helminth parasites stimulate Treg generation in the intestinal tract (18). In the case of the small intestinal mouse parasite H. polygyrus, de novo Foxp3 expression can be induced by its secretory products (HES), which is dependent on signaling through T cell TGF-βR (14). Short-chain fatty acids (SCFA), end products of bacteria-mediated fermentation of dietary fibers, can induce IL-10-producing Tregs in the colonic lamina propria (98-100). Particular species of bacteria, such as B. fragilis, or select Clostridium spp., can induce Tregs in the colonic lamina propria (5, 7, 8, 107). Treg induction by B. fragilis is dependent on the production of B. fragilis polysaccharide A (PSA) and the expression of T cell TLR2 (5, 107), and Treg induction by Clostridium spp. is though to be, at least in part, due to the stimulation of TGF-β secretion by intestinal epithelial cells (7, 8). Many additional bacterial microbiota species are capable of inducing Treg generation in the intestinal lamina propria (17, 108), and it is likely a combination of signals from the microbiota and macrobionts such as helminth parasites together maintain a tolerogenic intestinal environment.

Figure 2. Proposed mechanisms by which intestinal helminths and bacterial microbiota bi-directionally influence persistence in the mammalian host

It has recently become clear that intestinal helminth parasites and members of the bacterial microbiota influence one another’s ability to persist in the mammalian intestinal tract. The mechanisms by which they do so are likely multifactorial, site, and context dependent, and likely include direct as well as indirect effects on each other.