Type I interferons regulate immune responses in humans with blood-stage Plasmodium falciparum infection

de Oca, Marcela Montes, Kumar, Rajiv, Rivera, Fabian de Labastida, Amante, Fiona H., Sheel, Meru, Faleiro, Rebecca J., Bunn, Patrick T., Best, Shannon E., Beattie, Lynette, Ng, Susanna S., Edwards, Chelsea L., Boyle, Glen M., Price, Ric N., Anstey, Nicholas M., Loughland, Jessica R., Burel, Julie, Doolan, Denise, Haque, Ashraful, McCarthy, James S., and Engwerda, Christian R. (2016) Type I interferons regulate immune responses in humans with blood-stage Plasmodium falciparum infection. Cell Reports, 17 (2). pp. 399-412.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview
View at Publisher Website: http://dx.doi.org/10.1016/j.celrep.2016....
 
20
11


Abstract

The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing antiparasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4(+) T cell IFN gamma production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.

Item ID: 46511
Item Type: Article (Refereed Research - C1)
Keywords: malaria; type I interferons; CD4+ T cells; immune regulation; Tr1 cells; Th1 cells
Additional Information:

© 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

ISSN: 2211-1247
Funders: National Health and Medical Research Council of Australia (NHMRC), University of Queensland (UQ), Indian Department of Biotechnology (IDB)
Projects and Grants: IDB Inspire Fellowship
Date Deposited: 23 Nov 2016 07:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111716 Preventive Medicine @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
Downloads: Total: 11
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page