Malaria modifies neonatal and early-life toll-like receptor cytokine responses

Komi Gbédandé, Stefania Varani, Samad Ibitokou, Parfait Houngbegnon, Sophie Borgella, Odilon Nouatin, Sem Ezinmegnon, Adicatou laï Adeothy, Gilles Cottrell, Achille Massougbodji, Kabirou Moutairou, Marita Troye-Blomberg, Philippe Deloron, Nadine Fievet, Adrian J.F. Luty

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Protection 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. Plasmodium falciparum causes pregnancy-associated malaria (PAM), and epidemiological studies have shown that PAM enhances infants' susceptibility to infection with P. falciparum. We investigated how PAM-mediated exposures in utero affect innate immune responses and their relationship with infection in infancy. In a prospective study of mothers and their babies in Benin, we investigated changes in Toll-like receptor (TLR)-mediated cytokine responses related to P. falciparum infections. Whole-blood samples from 134 infants at birth and at 3,6, and 12 months of age were stimulated with agonists specific for TLR3, TLR4, TLR7/8, and TLR9. TLR-mediated interleukin 6 (IL-6) and IL-10 production was robust at birth and then stabilized, whereas tumor necrosis factor alpha (TNF-a) and gamma interferon (IFN-7) responses were weak at birth and then increased. In multivariate analyses, maternal P. falciparum infections at delivery were associated with significantly higher TLR3-mediated IL-6 and IL-10 responses in the first 3 months of life (P < 0.05) and with significantly higher TLR3-, TLR7/8-, and TLR9-mediated TNF-a responses between 6 and 12 months of age (P < 0.05). Prospective analyses showed that higher TLR3-and TLR7/8-mediated IL-10 responses at birth were associated with a significantly higher risk of P. falciparum infection in infancy (P < 0.05). Neonatal and infant intracellular TLR-mediated cytokine responses are conditioned by in utero exposure through PAM late in pregnancy. Enhanced 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.

Original languageEnglish (US)
Pages (from-to)2686-2696
Number of pages11
JournalInfection and immunity
Volume81
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Gbédandé, K., Varani, S., Ibitokou, S., Houngbegnon, P., Borgella, S., Nouatin, O., Ezinmegnon, S., Adeothy, A. L., Cottrell, G., Massougbodji, A., Moutairou, K., Troye-Blomberg, M., Deloron, P., Fievet, N., & Luty, A. J. F. (2013). Malaria modifies neonatal and early-life toll-like receptor cytokine responses. Infection and immunity, 81(8), 2686-2696. https://doi.org/10.1128/IAI.00237-13