title: At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells.
abstract: Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4(+) and CD8(+) T cells in filaria-infected (Fil(+)) and -uninfected (Fil(-)) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4(+) lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil(+), as were those of IL-10(+)/IL-4(+) double-producing CD4(+) cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil(+) compared to Fil(-) individuals. Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly produced by CD4(+)CD25(-) cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10-producing aTreg/Tr1s in Fil(+). Together, these data show that at steady state, IL-10-producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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: Siaka Y
authors.initials: SY
authors.lastname: Coulibaly
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: 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: D056704:Adaptive Immunity; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004605:Elephantiasis, Filarial / Q000276:immunology*; D017229:Enterobiasis / Q000276:immunology; D004757:Enterobius / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D006925:Hymenolepiasis / Q000276:immunology; D048189:Hymenolepis nana / Q000276:immunology; D008366:Mansonella / Q000276:immunology; D008368:Mansonelliasis / Q000276:immunology*; D008842:Microfilariae / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014958:Wuchereria bancrofti / Q000276:immunology
chemical_list: D016207:Cytokines