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

Author:
Ritter, Manuel, Krupp, Vanessa, Wiszniewsky, Katharina, Wiszniewsky, Anna, Katawa, Gnatoulma, Tamadaho, Ruth S. E., Hoerauf, Achim, Layland, Laura E.
Source:
Parasitology research 2018 v.117 no.8 pp. 2665-2675
ISSN:
0932-0113
Subject:
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
Abstract:
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.
Agid:
6055956