Anti-Interleukin-10 Unleashes Transcriptional Response to Leishmanial Antigens in Visceral Leishmaniasis Patients.

Affiliation

Singh OP(1)(2), Syn G(3), Nylén S(4), Engwerda C(5), Sacks D(6), Wilson ME(7), Kumar R(1)(8), Chakravarty J(1), Sundar S(1), Blackwell JM(3)(9), Fakiola M(9)(10).
Author information:
(1)Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
(2)Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
(3)Telethon Kids Institute, The University of Western Australia, Nedlands, Western Australia, Australia.
(4)Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
(5)QIMR Berghofer Medical Research Institute, Brisbane, Australia.
(6)Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes for Health, Bethesda, Maryland, USA.
(7)Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
(8)Centre for Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
(9)Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
(10)National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," Milan, Italy.

Abstract

Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon-γ and tumor necrosis factor in response to soluble leishmanial antigen (SLA) in whole-blood assays. Using transcriptional profiling, we demonstrate the impact of interleukin-10 (IL-10), a cytokine implicated in VL, on this response. SLA stimulation identified 28 differentially expressed genes (DEGs), 17/28 in a single network with TNF as hub. SLA plus anti-IL-10 produced 454 DEGs, 292 in a single network with TNF, IFNG, NFKBIA, IL6, and IL1B as hubs in concert with a remarkable chemokine/cytokine storm. Our data demonstrate the singular effect of IL-10 as a potent immune modulator in VL.