Helminth-mediated disease tolerance in TB: A role for microbiota?

Intestinal helminth infections are most prevalent in peri-equatorial regions of the world and have an overlapping geographical distribution with Mycobacterium tuberculosis (Mtb) infection—the causative agent of tuberculosis (TB). Importantly, approximately 40% of TB patients are asymptomatically infected with helminth parasites. While experimental and epidemiological evidence suggest that helminth infections alter the course of TB, other studies do not support this link [1]. Although the direct immunomodulatory effects of helminth infections on adaptive host immunity have been studied extensively, these can only partially explain the complex nature of helminth–TB interactions. Indeed, the potent immunomodulatory abilities of helminths may even reduce TB-associated tissue pathology [1] and contribute to disease tolerance [2]. However, helminth infections also induce changes to the gut microbiota that can have a systemic impact on heterologous infectious diseases [3]. Given previous studies demonstrating that the gut microbiota can shape disease tolerance to pulmonary infections [4], here, we discuss the current understanding of how the gut microbiota impacts TB and posit that helminth-mediated changes to this vast microbial community may contribute to the clinical course of TB in co-endemic regions (Fig 1). Open in a separate window Fig 1 Helminth infections, eliciting robust type 2 immune responses, might contribute to Mtb disease tolerance by inhibiting type 1 and type 3 immune responses, thus reducing inflammation and pathology while maintaining bacterial burden. An alternative, but not mutually exclusive, possibility is that helminth-mediated changes to the gut microbiota shape TB outcomes. The robust regulatory capacity of the gut microbiota (via immune suppression, metabolite processing, and niche competition) is an appealing mechanism to explain the contradicting data regarding the exact role of helminth infections in TB disease progression and disease tolerance in asymptomatic infected patients. This figure was created with BioRender.com. Mtb, Mycobacterium tuberculosis; TB, tuberculosis.