Plasmodium vivax infection impairs regulatory T-Cell suppressive function during acute malaria

Costa, P. A.C., Figueiredo, M. M., Diniz, S. Q., Peixoto, A. P.M.M., Maloy, K. J. , Teixeira-Carvalho, A., Tada, M. S., Pereira, D. B., Gazzinelli, R. T. and Antonelli, L. R.V. (2018) Plasmodium vivax infection impairs regulatory T-Cell suppressive function during acute malaria. Journal of Infectious Diseases, 218(8), pp. 1314-1323. (doi: 10.1093/infdis/jiy296) (PMID:29800313) (PMCID:PMC6129110)

Abstract

The balance between pro- and antiinflammatory mechanisms is essential to limit immune-mediated pathology, and CD4+ forkhead box P3 (Foxp3+) regulatory T cells (Treg) play an important role in this process. The expression of inhibitory receptors regulates cytokine production by Plasmodium vivax-specific T cells. Our goal was to assess the induction of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen (CTLA-4) on Treg during malaria and to evaluate their function. We found that P. vivax infection triggered an increase in circulating Treg and their expression of CTLA-4 and PD-1. Functional analysis demonstrated that Treg from malaria patients had impaired suppressive ability and PD-1+Treg displayed lower levels of Foxp3 and Helios, but had higher frequencies of T-box transcription factor+ and interferon-gamma+ cells than PD-1−Treg. Thus malaria infection alters the function of circulating Treg by triggering increased expression of PD-1 on Treg that is associated with decreased regulatory function and increased proinflammatory characteristics.

• Item Type: Articles
• Additional Information: This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant number PQ-307408/2016-7); Fundação de Amparo à Pesquisa do Estado de Minas Gerais (grant number APQ-00616-16); CNPq/FAPEMIG-National Institute of Science and Technology for Vaccines (grant number CNPq-573547/2008-4/FAPEMIG/MS-CBB-APQ00077-09); FAPEMIG, PRONEX-Malaria (grant number CBB-APQ-01355-14); National Institute of Allergy and Infectious Diseases (grant number NIH/NIAID/ICEMR/U19 AI089681); CNPq/Ciencias sem fronteiras (grant number 402553/2012–8); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maloy, Professor Kevin
• Authors: Costa, P. A.C., Figueiredo, M. M., Diniz, S. Q., Peixoto, A. P.M.M., Maloy, K. J., Teixeira-Carvalho, A., Tada, M. S., Pereira, D. B., Gazzinelli, R. T., and Antonelli, L. R.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Infectious Diseases
• Publisher: Oxford University Press
• ISSN: 0022-1899
• ISSN (Online): 1537-6613
• Published Online: 24 May 2018