Credit: GETTY

The majority of helminth infections worldwide are concentrated in developing nations, where other diseases such as tuberculosis are endemic. It is known that a pre-existing helminth infection can impinge on immunity to Mycobacterium tuberculosis infection, but the underlying mechanism has yet to be described. Potian et al. now show that interleukin-4 (IL-4) production induced by infection with the helminth Nippostrongylus brasiliensis enhances the persistence of M. tuberculosis infection in mice, at least in part through the alternative activation of macrophages in the lung.

Infection of mice with N. brasiliensis (which transiently migrates through the lung during its life cycle) was found to induce a strong IL-4 response that impaired resistance to subsequent M. tuberculosis infection. Surprisingly, M. tuberculosis-specific T helper 1 (TH1) cell responses were similar in the draining lymph nodes of mice with or without N. brasiliensis infection. So, the authors next examined the phenotype of macrophages in the lungs of co-infected mice and found an increase in the expression of markers of alternatively activated macrophages (which have been shown to be compromised in their ability to control M. tuberculosis infection).

Furthermore, in the absence of IL-4 receptor subunit-α (IL-4Rα), co-infected mice did not have an increased bacterial burden or an accumulation of alternatively activated macrophages in their lungs. Transfer of wild-type macrophages to N. brasiliensis-infected Il4ra−/− mice resulted in increased bacterial burden following M. tuberculosis infection, indicating that the IL-4-mediated alternative activation of macrophages contributes to reduced anti-tuberculosis immunity.

So, the IL-4Rα-dependent increase in the number of alternatively activated macrophages in response to helminth infections can, at least in part, compromise protection against M. tuberculosis.