At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells.
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.
Metenou
Simon
S
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Dembele
Benoit
B
Konate
Siaka
S
Dolo
Housseini
H
Coulibaly
Siaka Y
SY
Coulibaly
Yaya I
YI
Diallo
Abdallah A
AA
Soumaoro
Lamine
L
Coulibaly
Michel E
ME
Sanogo
Dramane
D
Doumbia
Salif S
SS
Traoré
Sekou F
SF
Mahanty
Siddhartha
S
Klion
Amy
A
Nutman
Thomas B
TB
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
D016207:Cytokines