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

Author:

Singh Om Prakash12,Syn Genevieve3,Nylén Susanne4,Engwerda Christian5,Sacks David6,Wilson Mary E7,Kumar Rajiv18,Chakravarty Jaya1,Sundar Shyam1,Blackwell Jenefer M39,Fakiola Michaela910

Affiliation:

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

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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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