Iron acts as a second signal during coinfection with M. tuberculosis and N. brasiliensis leading to exacerbated M. tuberculosis disease outcome (MPF1P.769)

Previously, our laboratory has demonstrated that N. brasiliensis (Nb), an intestinal helminth, is able to exacerbate Mtb burden in coinfected Balb/c mice through generation of alternatively activated macrophages (AAMs). To examine the role of host genetic background in infection we performed coinfection experiments in C57Bl/6 mice. In contrast to Balb/c, coinfected C57Bl/6 mice were able to control Mtb burden comparable to mice infected with Mtb alone, despite mounting a Th2 response. This led us to hypothesize that a factor in addition to the generation of AAMs was responsible for the increased Mtb burden seen in the coinfection model. Concurrent experiments designed to understand Mtb survival within in vitro derived AAMs showed that IL-4 and IL-13 treatment was insufficient to cause differences in Mtb growth, compared to untreated macrophages. However the addition of iron significantly increased Mtb growth in AAMs. Iron, besides being important for Mtb growth; is also present in the lungs following tissue damage caused by Nb larval migration. To determine the role of iron during Nb infection we evaluated the expression of iron responsive genes in the murine lungs at 3, 5, and 7 days post infection. Balb/c and C57Bl/6 mice exhibited distinct profiles in response to Nb infection consistent with iron recycling and iron sequestration, respectively. Future studies aim to further understand the role of iron as important cofactor in regulating bacterial burden during coinfection.