Enrichment of IFN-γ producing cells in different murine adipose tissue depots upon infection with an apicomplexan parasite.

Luzia Teixeira,Alexandra Correia,Raquel M Marques,Pedro Ferreirinha,Joana Melo,João Moreira,Ana Pinto,Filipa Bezerra,Paula G Ferreira,Manuel Vilanova

doi:10.1038/srep23475

Abstract

Here we report that lean mice infected with the intracellular parasite Neospora caninum show a fast but sustained increase in the frequency of IFN-γ-producing cells noticeable in distinct adipose tissue depots. Moreover, IFN-γ-mediated immune memory could be evoked in vitro in parasite antigen-stimulated adipose tissue stromal vascular fraction cells collected from mice infected one year before. Innate or innate-like cells such as NK, NK T and TCRγδ+ cells, but also CD4+ and CD8+ TCRβ+ lymphocytes contributed to the IFN-γ production observed since day one of infection. This early cytokine production was largely abrogated in IL-12/IL23 p40-deficient mice. Moreover, production of IFN-γ by stromal vascular fraction cells isolated from these mice was markedly lower than that of wild-type counterparts upon stimulation with parasite antigen. In wild-type mice the increased IFN-γ production was concomitant with up-regulated expression of genes encoding interferon-inducible GTPases and nitric oxide synthase, which are important effector molecules in controlling intracellular parasite growth. This increased gene expression was markedly impaired in the p40-deficient mice. Overall, these results show that NK cells but also diverse T cell populations mediate a prompt and widespread production of IFN-γ in the adipose tissue of N. caninum infected mice.

Highlights

T cells[24,25]; invariant natural killer T (NKT) cells[26], γ δ T cells[27] and natural killer (NK) cells[5]
CD8+ TCRβ + and CD4+ TCRβ + cells were found to be early producers of IFN-γ in the infected mice, as detected in most adipose tissue depots analysed (Fig. 1d,e and Supplementary Fig. S2). To this widespread cellular immune response detected in the gonadal, mesenteric and subcutaneous adipose tissue (GAT, MAT and SAT, respectively), only NK and CD4+ T cells produced IFN-γ in the mesenteric lymph nodes (MLN) of infected mice at frequencies higher than those detected in controls (Fig. 1a,e)
The IL-12/IL-23 p40-dependent early production of IFN-γ in the adipose tissue was not confined to the CD8+ T cell population as it was abrogated for NK T, TCRγ δ +, and CD4+ T cells in infected p40−/− mice

Summary

Introduction

T cells[24,25]; invariant natural killer T (NKT) cells[26], γ δ T cells[27] and natural killer (NK) cells[5]. We aimed here at determining whether production of IFN-γ could be promoted upon infection in distinct adipose tissue depots and which cell types could be the source of this cytokine. The obtained results show that distinct lymphoid cell populations in both visceral and subcutaneous adipose tissue contribute to IFN-γ production and that local early production of this cytokine is largely dependent on IL-12/IL-23 p40. Interestingly, they show that parasite-specific memory as revealed by IFN-γ production is maintained in the adipose tissue at least for one year upon the infectious challenge

Methods

Results

Conclusion