Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria

PLoS Pathogens

Mary K Muhindo¹  Prasanna Jagannathan²  Margaret E. Feeney³  Michelle J. Boyle⁴  Emmanuel Arinaitwe⁴  Felistas Nankya⁴  Ijeoma Eccles-James⁴  Lila A. Farrington⁴  Hilary M. Vance⁴  Samuel Wamala⁴  Katherine Bowen⁴  Moses R. Kamya⁴  John Rek⁵  Agaba Katureebe⁵  Grant Dorsey⁵  Kate Naluwu⁵  Tara I McIntyre⁵  Esther Sikyomu⁵  Ann Auma⁵  Mayimuna Nalubega⁵  Jordan Tappero⁵  James Kapisi⁵  Victor Bigira⁵  Bryan Greenhouse⁵ 

[1] CDC, Atlanta, Georgia, United States of America;Center for Biomedical Research, The Burnet Institute, Melbourne, Australia;Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;Department of Medicine, University of California San Francisco, San Francisco, California, United States of America;Infectious Diseases Research Collaboration, Kampala, Uganda

关键词: Regulatory T cells;    Malaria;    Malarial parasites;    Parasitic diseases;    Plasmodium;    Children;    Prisms;    Apoptosis;   

DOI  :  10.1371/journal.ppat.1005041

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations.

【 授权许可】

CC BY