Helminth-Tuberculosis Co-infection: An Immunologic Perspective

Abstract

Over 2 billion people worldwide are infected with helminths (worms). Similarly, infection with Mycobacterium tuberculosis (Mtb) occurs in over a third of the world's population, often with a great degree of geographical overlap with helminth infection. Interestingly, the responses induced by the extracellular helminths and those induced by the intracellular Mtb are often mutually antagonistic and, as a consequence, can result in impaired (or cross-regulated) host responses to either of the infecting pathogens. In this review, we outline the nature of the immune responses induced by infections with helminths and tuberculosis (TB) and then provide data from both experimental models and human studies that illustrate how the immune response engendered by helminth parasites modulates Mtb-specific responses in helminth-TB co-infection.

Inhibition of IL‐17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

“…17 This suggests that infection susceptibility to extracellular fungi such as C. albicans is likely a result of a combination of factors rather than a deficiency of just one cytokine, a situation likely to apply as well for host resistance to intracellular pathogens such as M. tuberculosis. [19][20][21][22]61,64 In summary, the absence of TB reactivation in secukinumab clinical studies 17 (and further detailed here) is moreover supported by experimental in vitro studies showing lack of effect of secukinumab on M. tuberculosis dormancy in a human in vitro microgranuloma model (this study), and lack of compromised host resistance in anti-IL-17A-treated M. tuberculosis-infected mice. 37 Collecting real-world evidence data, through registries, will be an opportunity to further substantiate the safety of secukinumab in this regard.…”

Intestinal nematode infection exacerbates experimental visceral leishmaniasis

“…Single infection with L donovani induced expression of a mixture of type 1, type 2 and regulatory transcripts in livers, with strongest impact on type 1 genes (Figure D). iNOS and subsequent NO generation by macrophages is fundamental for control of intracellular pathogens of macrophages in mice . In line with a higher parasite burden, nos2 expression was reduced in livers of coinfected mice compared to the single L donovani ‐infected mice (Figure D,E).…”

“…It has been shown that control and susceptibility of murine Leishmania donovani infection correlate well with generation of type 1 responses or lack thereof, respectively . Notably, intestinal worm infections are most common in poor rural areas, often geographically overlapping with areas that are endemic for leishmaniasis …”

“…6 Notably, intestinal worm infections are most common in poor rural areas, often geographically overlapping with areas that are endemic for leishmaniasis. [6][7][8] Mice are natural hosts for Heligmosomoides polygyrus-a strictly intestinal nematode that has become a well-established model for studies on the effects of chronic intestinal helminth infection on the host. 1,9 Heligmosomoides polygyrus induces a strong type 2 response that can be measured in mesenteric lymph nodes, Peyer's patches and lamina propria during the first weeks after infection.…”

Topological data analysis to model the shape of immune responses during co-infections

“…Co-infections have effects on health at multiple levels: Co-infections can increase or decrease the rate of transmission of other infections [3] , modulate the host immune response [4] , create protection and resilience or susceptibility to further infections [5,6] , alter the performance of diagnostic tests and antimicrobial chemotherapy [7,8] , and even create opportunities for the emergence of new pathogens [9,10] . In other words, some co-infections can have detrimental, or even beneficial, outcomes.…”