Helminth-driven type 2 inflammation enhances CD8+ T cell-mediated control of acute gammaherpesvirus infection

The first stages of host colonisation with pathogens often determine the efficacy of their control through priming and maintenance of effective adaptive immune responses, which are essential for such control. Infection with different pathogens often occurs concurrently and a better understanding of how our immune system faces multiple aggressions with different sorts of pathogens is therefore important. In this study, we have investigated how helminth-driven Th2-type inflammation affects the control of host colonization by a gammaherpesvirus. We used in vivo imaging of murid herpesvirus 4 (MuHV-4) live infection to investigate viral replication in mice and observed that pre-exposed mice to helminth (Schistosoma mansoni or Nippostrongylus brasiliensis) better controlled lung acute infection and weight loss. The improved control of acute infection was associated with increased virus-specific effector CD8+ T cell responses in the bronchoalveolar lavage, lung, draining LN (dLN) and spleen; whereas depletion of CD8+ cells caused a loss of viral infection control irrespective of helminth exposure. Exposure to S. mansoni eggs caused increased numbers of dendritic cells (DCs), predominantly CD11b+ conventional DCs in the lung, and in the dLN, which was associated with higher numbers of antigen-loaded lung DCs migrating to the dLN after MuHV-4 infection. These results suggested that S. mansoni egg-induced inflammation might result in an improved priming of virus-specific CD8+ T cells. To address the role of type 2 inflammation, we next used interleukin 4 receptor α-chain (IL-4Rα) deficient mice exposed to S. mansoni eggs and observed the absence of both the enhanced control of viral acute infection and the increased CD8+ T cell response, suggesting that IL-4Rα signalling is involved. Collectively, we present data indicating that IL-4Rα-dependent type 2 inflammation induced in the lung by helminth exposure improves host control of acute viral infection through the induction of an increased virus-specific cytotoxic T cell effector response.