Hidden Consequences of Living in a Wormy World: Nematode‐Induced Immune Suppression Facilitates Tuberculosis Invasion in African Buffalo

Abstract

Most hosts are infected with multiple parasites, and responses of the immune system to co-occurring parasites may influence disease spread. Helminth infection can bias the host immune response toward a T-helper type 2 (Th2) over a type 1 (Th1) response, impairing the host’s ability to control concurrent intracellular microparasite infections and potentially modifying disease dynamics. In humans, immune-mediated interactions between helminths and microparasites can alter host susceptibility to diseases such as HIV, tuberculosis (TB), and malaria. However, the extent to which similar processes operate in natural animal populations and influence disease spread remains unknown. We used cross-sectional, experimental, and genetic studies to show that gastrointestinal nematode infection alters immunity to intracellular microparasites in free-ranging African buffalo (Syncerus caffer). Buffalo that were more resistant to nematode infection had weaker Th1 responses, there was significant genotypic variation in nematode resistance, and anthelminthic treatment enhanced Th1 immunity. Using a disease dynamic model parameterized with empirical data, we found that nematode-induced immune suppression can facilitate the invasion of bovine TB in buffalo. In the absence of nematodes, TB failed to invade the system, illustrating the critical role nematodes may play in disease establishment. Our results suggest that helminths, by influencing the likelihood of microparasite invasion, may influence patterns of disease emergence in the wild.

Host and parasite diversity jointly control disease risk in complex communities

“…Antagonistic effects among parasites could result from competition for a shared resource (e.g., space or host cells) or interactions mediated through host immunity (7). Based on the differences in infection sites among the parasites included here and their low metabolic demands within second intermediate hosts, cross-reactive immunity is perhaps the most probable mechanism, consistent with a growing emphasis on the role of host immunity in determining coinfection outcomes (31,(33)(34)(35)(36). That host diversity generally had stronger inhibitory effects on parasite loads than did parasite diversity may stem from the greater potential for low-competence hosts to function as population sinks for invading parasites, whereas immune-mediated competition associated with coinfection acts primarily to weaken persistence of parasites that have already colonized (2,37).…”

“…Divergent lines of inquiry into the influence of both host diversity (2,15,30) and parasite coinfections (10,27,31) have gained considerable momentum in disease ecology research over the past decade, but thus far few studies have simultaneously integrated these topics. Here, we combined results from field surveys, a simplified laboratory experiment, and a more realistic outdoor mesocosm experiment to evaluate the relationships among host diversity, parasite diversity, and transmission.…”

“…Although an increasing number of studies have reported negative correlations between host diversity and disease risk (29,38,39), the hidden effects of concurrent changes in parasite communities have rarely been explored (19,31,40). Future studies examining the biodiversity-disease relationship should focus more heavily on the relative importance of multiple components of biodiversity (and how they covary) in driving observed patterns in disease risk (41)(42)(43), including the direct and indirect effects of hosts, nonhosts (e.g., predators and competitors), parasites, as well as other microorganisms.…”

Reciprocal Interaction Matrix Reveals Complex Genetic and Dose-Dependent Specificity among Coinfecting Parasites

“…In general, interactions among coinfecting parasites can take place through direct competition (Patrick 1991;Selva et al 2009;Staves and Knell 2010) and/or indirectly through host defenses (Adams et al 1989;Rå-berg et al 2006;Ezenwa et al 2010;Laine 2011). In most study systems, separation between these mechanisms is difficult.…”

INFECTION OF C57BL/6 MICE BYTRYPANOSOMA MUSCULIMODULATES HOST IMMUNE RESPONSES DURINGBRUCELLA ABORTUSCOCOLONIZATION

“…A recent example includes the African buffalo (Syncerus caffer), which has seen an emergence of bovine tuberculosis linked to nematode immunosuppression. The mechanism described is a shift toward a Th2-dominated response, driven by helminth immune suppression, leading to favorable colonization conditions for tuberculosis (Ezenwa et al 2010). Studies such as these complement the earlier experimental study describing a Trypanosoma-induced immune suppression effect on Trichinella worm burdens and decreased vaccine efficacy (Onah and Wakelin 2000).…”