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Absence of IL-17A in Litomosoides sigmodontis-infected mice influences worm development and drives elevated filarial-specific IFN-γ

Ritter, Manuel, Krupp, Vanessa, Wiszniewsky, Katharina, Wiszniewsky, Anna, Katawa, Gnatoulma, Tamadaho, Ruth S. E., Hoerauf, Achim, Layland, Laura E.
Parasitology research 2018 v.117 no.8 pp. 2665-2675
CD4-positive T-lymphocytes, Litomosoides sigmodontis, adults, blindness, chemokine CCL11, chemokine CCL17, climate, humans, immune response, interferon-gamma, interleukin-17, interleukin-21, interleukin-4, interleukin-6, lymph nodes, mice, onchocerciasis, parasites, public health, secretion, socioeconomics, thoracic cavity, tropical diseases
Lymphatic filariasis, onchocerciasis and loiasis are widespread neglected tropical diseases causing serious public health problems and impacting the socio-economic climate in endemic communities. More than 100 million people currently suffer from filarial infections but disease-related symptoms and infection-induced immune mechanisms are still ambiguous. Although most infected individuals have dominant Th2 and regulatory immune responses leading to a homeostatic regulated state, filarial-induced overt pathology like lymphedema, dermal pathologies or blindness can occur. Interestingly, besides dominant Th2 and regulatory T cell activation, increased Th17-induced immune responses were associated with filarial infection and overt helminth-induced pathology in humans. However, the immunological mechanisms of Th17 cells and the release of IL-17A during filarial infections remain unclear. To decipher the role of IL-17A during filarial infection, we naturally infected IL-17A⁻/⁻ and wildtype C57BL/6 mice with the rodent filariae Litomosoides sigmodontis and analysed parasite development and immune alterations. Our study reveals that infected IL-17A-deficient C57BL/6 mice present reduced worm burden on days 7 and 28 p.i. but had longer adult worms on day 28 p.i. in the thoracic cavity (TC), the site of infection. In addition, infiltration of CD4⁺ T cells, CD4⁺Foxp3⁺ regulatory T and functional CD4⁺Rorγt⁺pStat3⁺ Th17 cells in the TC was reduced in IL-17A-deficient mice accompanied by reduced eotaxin-1 and CCL17 levels. Furthermore, mediastinal lymph node cells isolated from IL-17A⁻/⁻ mice showed increased filarial-specific IFN-γ but not IL-4, IL-6, or IL-21 secretion. This study shows that Th17 signalling is important for host immune responses against filarial infection but appears to facilitate worm growth in those that reach the TC.