@article{PAR00010718,
  title = {{M}alaria modifies nonatal and early-life toll-like receptor cytokine responses},
  author = {{G}bedande, {K}. and {V}arani, {S}. and {I}bitokou, {S}. and {H}oungbegnon, {P}. and {B}orgella, {S}. and {N}ouatin, {O}. and {E}zinmegnon, {S}. and {A}deothy, {A}. {I}. and {C}ottrell, {G}illes and {M}assougbodji, {A}. and {M}outairou, {K}. and {T}roye-{B}lomberg, {M}. and {D}eloron, {P}hilippe and {F}ievet, {N}adine and {L}uty, {A}drian},
  editor = {},
  language = {{ENG}},
  abstract = {{P}rotection from infections in early life relies extensively on innate immunity, but it is unknown whether and how maternal infections modulate infants' innate immune responses, thereby altering susceptibility to infections. {P}lasmodium falciparum causes pregnancy-associated malaria ({PAM}), and epidemiological studies have shown that {PAM} enhances infants' susceptibility to infection with {P}. falciparum. {W}e investigated how {PAM}-mediated exposures in utero affect innate immune responses and their relationship with infection in infancy. {I}n a prospective study of mothers and their babies in {B}enin, we investigated changes in {T}oll-like receptor ({TLR})-mediated cytokine responses related to {P}. falciparum infections. {W}hole-blood samples from 134 infants at birth and at 3, 6, and 12 months of age were stimulated with agonists specific for {TLR}3, {TLR}4, {TLR}7/8, and {TLR}9. {TLR}-mediated interleukin 6 ({IL}-6) and {IL}-10 production was robust at birth and then stabilized, whereas tumor necrosis factor alpha ({TNF}-alpha) and gamma interferon ({IFN}-gamma) responses were weak at birth and then increased. {I}n multivariate analyses, maternal {P}. falciparum infections at delivery were associated with significantly higher {TLR}3-mediated {IL}-6 and {IL}-10 responses in the first 3 months of life ({P}<0.05) and with significantly higher {TLR}3-, {TLR}7/8-, and {TLR}9-mediated {TNF}-alpha responses between 6 and 12 months of age ({P}<0.05). {P}rospective analyses showed that higher {TLR}3- and {TLR}7/8-mediated {IL}-10 responses at birth were associated with a significantly higher risk of {P}. falciparum infection in infancy ({P}<0.05). {N}eonatal and infant intracellular {TLR}-mediated cytokine responses are conditioned by in utero exposure through {PAM} late in pregnancy. {E}nhanced {TLR}-mediated {IL}-10 responses at birth are associated with an increased risk of {P}. falciparum infection, suggesting a compromised ability to combat infection in early life.},
  keywords = {},
  booktitle = {},
  journal = {{I}nfection and {I}mmunity},
  volume = {81},
  numero = {8},
  pages = {2686--2696},
  ISSN = {0019-9567},
  year = {2013},
  DOI = {10.1128/iai.00237-13},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00010718},
}