Neither Primary nor Memory Immunity to Mycobacterium tuberculosis Infection Is Compromised in Mice with Chronic Enteric Helminth Infection

Abstract

bPreviously we had reported that Nippostrongylus brasiliensis, a helminth with a lung migratory phase, affected host resistance against Mycobacterium tuberculosis infection through the induction of alternatively activated (M2) macrophages. Several helminth species do not have an obligatory lung migratory phase but establish chronic infections in the host that include potent immune downregulatory effects, in part mediated through induction of a FoxP3 ؉ T regulatory cell (Treg) response. Treg cells exhibit duality in their functions in host defense against M. tuberculosis infection since their depletion leads to enhanced priming of T cells in the lymph nodes and attendant improved control of M. tuberculosis infection, while their presence in the lung granuloma protects against excessive inflammation. Heligmosomoides polygyrus is a strictly murine enteric nematode that induces a strong FoxP3 Treg response in the host. Therefore, in this study we investigated whether host immunity to M. tuberculosis infection would be modulated in mice with chronic H. polygyrus infection. We report that neither primary nor memory immunity conferred by Mycobacterium bovis BCG vaccination was affected in mice with chronic enteric helminth infection, despite a systemic increase in FoxP3؉ T regulatory cells. The findings indicate that anti-M. tuberculosis immunity is not similarly affected by all helminth species and highlight the need to consider this inequality in human coinfection studies.

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

“…Interestingly, while helminth coinfections increase M. bovis BCG (11) and Mtb (27) lung burden, the increase in mycobacterial burden is often transient (27) and moderate (about 1 log higher in coinfected hosts) (11,27), suggesting that the effect of helminth coinfections on Mtb control is not profound enough to fully explain the increased severity of TB in helminth-coinfected individuals observed in TB endemic regions. Furthermore, in some models of helminth/Mtb coinfection, there are no differences observed in overall mycobacterial control (28,29). Our results support these published studies, as S. mansoni coinfection or immunization with SEA resulted in increased Mtb burden in the lung.…”

“…However, this effect was not profound, suggesting that Mtb control mechanisms are not completely suppressed in coinfected hosts. Furthermore, while some evidence suggests that Mtb-specific Th1 responses are impaired due to helminth coinfection (7,11,30), other studies have found that Mtb-specific Th1 responses are unaltered in the presence of helminth infections (27,29). Our studies show that Mtb infection induces a potent Th1 signature in in vivo primed T cells isolated Helminth infections are associated with increased TB reactivation rates in HIV-infected patients (10).…”

Intestinal nematode infection exacerbates experimental visceral leishmaniasis

“…These divergent results may have several explanations such as the choice of model, infectious dose and the time of infection/s. While there are studies indicating systemic dissemination of both type 2 and regulatory responses after intestinal nematode infection, the effects are most evident when worm burdens are high and when the worm itself is in proximity to the secondary challenge …”

Helminth-Tuberculosis Co-infection: An Immunologic Perspective

“…In one mouse study, infection with Toxocara canis was not associated with increased susceptibility to pulmonary tuberculosis [85]. Similarly, mice co-infected with N. braziliensis and M. bovis BCG were able to clear the BCG infection at the same rate as the helminth-uninfected controls [86]. Finally, a cotton rat model of Mtb-helminth co-infection also failed to detect an influence of the helminth on TB disease or bacterial burdens [87].…”