Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are Preferentially Activated during Acute Malaria in Children
Nyamekye Obeng-Adjei,
Silvia Portugal,
Tuan M. Tran,
Takele B. Yazew,
Jeff Skinner,
Shanping Li,
Aarti Jain,
Philip L. Felgner,
Ogobara K. Doumbo,
Kassoum Kayentao,
Aissata Ongoiba,
Boubacar Traore,
Peter D. Crompton
Affiliations
Nyamekye Obeng-Adjei
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Silvia Portugal
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Tuan M. Tran
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Takele B. Yazew
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Jeff Skinner
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Shanping Li
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Aarti Jain
Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA
Philip L. Felgner
Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA
Ogobara K. Doumbo
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako BP E.1805, Mali
Kassoum Kayentao
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako BP E.1805, Mali
Aissata Ongoiba
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako BP E.1805, Mali
Boubacar Traore
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako BP E.1805, Mali
Peter D. Crompton
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA
Malaria-specific antibody responses are short lived in children, leaving them susceptible to repeated bouts of febrile malaria. The cellular and molecular mechanisms underlying this apparent immune deficiency are poorly understood. Recently, T follicular helper (Tfh) cells have been shown to play a critical role in generating long-lived antibody responses. We show that Malian children have resting PD-1+CXCR5+CD4+ Tfh cells in circulation that resemble germinal center Tfh cells phenotypically and functionally. Within this population, PD-1+CXCR5+CXCR3− Tfh cells are superior to Th1-polarized PD-1+CXCR5+CXCR3+ Tfh cells in helping B cells. Longitudinally, we observed that malaria drives Th1 cytokine responses, and accordingly, the less-functional Th1-polarized Tfh subset was preferentially activated and its activation did not correlate with antibody responses. These data provide insights into the Tfh cell biology underlying suboptimal antibody responses to malaria in children and suggest that vaccine strategies that promote CXCR3− Tfh cell responses may improve malaria vaccine efficacy.
