Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response.

Naomi Aira,Robert Blomgran,Derek M Mckay,Anna-Maria Andersson,Susmita K Singh,Helton Da Costa Santiago

doi:10.1371/journal.pntd.0005390

Naomi Aira, Robert Blomgran + Show 4 more

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https://doi.org/10.1371/journal.pntd.0005390

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Abstract

BackgroundIn countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis.Principal findingsWe investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb.ConclusionWe conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.

Highlights

Infection with helminth parasites and microbial pathogens present very different challenges to the mammalian immune system, and distinct immune effector mechanisms have evolved to combat infection with these different classes of organisms
Independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages
We have recently shown that both M. tuberculosis H37Ra and H37Rv infect and can replicate in human monocyte-derived macrophages (hMDMs) ( H37Rv replicate to a greater extent), and that both the strains can manipulate/block the autophagy pathway [28]

Summary

Introduction

Infection with helminth parasites and microbial pathogens present very different challenges to the mammalian immune system, and distinct immune effector mechanisms have evolved to combat infection with these different classes of organisms. The geographic distribution of tuberculosis (TB) and endemic helminth infections are almost superimposable and many individuals with TB will be, or will have been, infected with helminth parasites [3,4,5]. Given the general paradigm of the reciprocal inhibition of Th1 and Th2 immune responses and increase in TB globally, a comprehensive understanding of the impact of infection with helminth parasites on the response to Mycobacterium tuberculosis (Mtb) and the outcome of TB is essential. Co-infection with helminth parasites and Mtb in mice and analysis of co-infected individuals has provided important, and often contrasting data, which may reflect host-parasite specificity in response to the helminths. A strong Th2 response has been associated with decreased protection against tuberculosis.

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