title: Filarial infection suppresses malaria-specific multifunctional Th1 and Th17 responses in malaria and filarial coinfections.
abstract: The mechanisms underlying the modulation of both the malaria-specific immune response and the course of clinical malaria in the context of concomitant helminth infection are poorly understood. We used multiparameter flow cytometry to characterize the quality and the magnitude of malaria-specific T cell responses in filaria-infected and -uninfected individuals with concomitant asymptomatic Plasmodium falciparum malaria in Mali. In comparison with filarial-uninfected subjects, filarial infection was associated with higher ex vivo frequencies of CD4(+) cells producing IL-4, IL-10, and IL-17A (p = 0.01, p = 0.001, and p = 0.03, respectively). In response to malaria Ag stimulation, however, filarial infection was associated with lower frequencies of CD4(+) T cells producing IFN-γ, TNF-α, and IL-17A (p < 0.001, p = 0.04, and p = 0.04, respectively) and with higher frequencies of CD4(+)IL10(+)T cells (p = 0.0005). Importantly, filarial infection was associated with markedly lower frequencies of malaria Ag-specific Th1 (p < 0.0001), Th17 (p = 0.012), and "TNF-α" (p = 0.0008) cells, and a complete absence of malaria-specific multifunctional Th1 cells. Filarial infection was also associated with a marked increase in the frequency of malaria-specific adaptive regulatory T/Tr1 cells (p = 0.024), and the addition of neutralizing anti-IL-10 Ab augmented the amount of Th1-associated cytokine produced per cell. Thus, among malaria-infected individuals, concomitant filarial infection diminishes dramatically the frequencies of malaria-specific Th1 and Th17 T cells, and alters the quality and magnitude of malaria-specific T cell responses.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. metenous@niaid.nih.gov
authors.forename: Simon
authors.initials: S
authors.lastname: Metenou
authors.forename: Benoit
authors.initials: B
authors.lastname: Dembele
authors.forename: Siaka
authors.initials: S
authors.lastname: Konate
authors.forename: Housseini
authors.initials: H
authors.lastname: Dolo
authors.forename: Yaya I
authors.initials: YI
authors.lastname: Coulibaly
authors.forename: Abdallah A
authors.initials: AA
authors.lastname: Diallo
authors.forename: Lamine
authors.initials: L
authors.lastname: Soumaoro
authors.forename: Michel E
authors.initials: ME
authors.lastname: Coulibaly
authors.forename: Siaka Y
authors.initials: SY
authors.lastname: Coulibaly
authors.forename: Dramane
authors.initials: D
authors.lastname: Sanogo
authors.forename: Salif S
authors.initials: SS
authors.lastname: Doumbia
authors.forename: Sekou F
authors.initials: SF
authors.lastname: Traoré
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mahanty
authors.forename: Amy
authors.initials: A
authors.lastname: Klion
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D015897:Comorbidity; D005260:Female; D005368:Filariasis / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D005370:Filarioidea / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008302:Mali / Q000453:epidemiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4