Journal article

Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome Is Associated With Dysregulation of IL-7/IL-7 Receptor Signaling Pathway in T Cells and Monocyte Activation

Ngomu Akeem Akilimali, Daniel M Muema, Charles Specht, Christina C Chang, Mahomed-Yunus S Moosa, Stuart M Levitz, Sharon R Lewin, Martyn A French, Thumbi Ndung'u

JAIDS Journal of Acquired Immune Deficiency Syndromes | LIPPINCOTT WILLIAMS & WILKINS | Published : 2019

Abstract

BACKGROUND: Systemic levels of interleukin (IL)-7 at antiretroviral therapy (ART) initiation have previously been shown to be predictive of HIV-linked paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). We therefore explored IL-7/IL-7 receptor (IL-7/IL-7R) signaling pathway dysfunction, with related alterations in immune function, as a mechanism underlying C-IRIS. METHOD: HIV-infected patients with cryptococcal meningitis who experienced C-IRIS (n = 27) were compared with CD4 T-cell count-matched counterparts without C-IRIS (n = 27), after antifungal therapy and pre-ART initiation. Flow cytometry was used to assess T-cell and monocyte phenotypes and fu..

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University of Melbourne Researchers

Grants

Awarded by Pfizer Neuroscience Grant


Awarded by Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship


Awarded by NHMRC


Awarded by sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative


Awarded by Wellcome Trust


Funding Acknowledgements

Supported by REACH Initiative (Research and Education in HIV/AIDS for Resource Poor Countries) (M.A.F.) and Pfizer Neuroscience Grant (NS052.10-C.C.C.). C.C.C. is supported by the Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship APP1092160. M.A.F. was supported by NHMRC grant 510448. S.R.L. is a NHMRC practitioner fellow APP1042654. T.N. was supported by grants from the Howard Hughes Medical Institute and by the South African Department of Science and Technology/National Research Foundation Research Chairs Initiative. Additional support for this study was provided by the Victor Daitz Foundation. This work was also supported in part through the sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant #DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant #107752/Z/15/Z] and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, or the UK government.