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

Komi Gbedande, Stefania Varani, Akanni Adededji Abdoul 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

23 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Toll-Like Receptors
Malaria
Plasmodium falciparum
Cytokines
Interleukin-10
Parturition
Pregnancy
Infection
Innate Immunity
Mothers
Interleukin-6
Tumor Necrosis Factor-alpha
Benin
Aptitude
Interferon-alpha
Interferon-gamma
Epidemiologic Studies
Multivariate Analysis
Prospective Studies

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Gbedande, K., Varani, S., Ibitokou, A. A. A., Houngbegnon, P., Borgella, S., Nouatin, O., ... 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

Malaria modifies neonatal and early-life toll-like receptor cytokine responses. / Gbedande, Komi; Varani, Stefania; Ibitokou, Akanni Adededji Abdoul; Houngbegnon, Parfait; Borgella, Sophie; Nouatin, Odilon; Ezinmegnon, Sem; Adeothy, Adicatou laï; Cottrell, Gilles; Massougbodji, Achille; Moutairou, Kabirou; Troye-Blomberg, Marita; Deloron, Philippe; Fievet, Nadine; Luty, Adrian J F.

In: Infection and Immunity, Vol. 81, No. 8, 08.2013, p. 2686-2696.

Research output: Contribution to journalArticle

Gbedande, K, Varani, S, Ibitokou, AAA, Houngbegnon, P, Borgella, S, Nouatin, O, Ezinmegnon, S, Adeothy, AL, Cottrell, G, Massougbodji, A, Moutairou, K, Troye-Blomberg, M, Deloron, P, Fievet, N & Luty, AJF 2013, 'Malaria modifies neonatal and early-life toll-like receptor cytokine responses', Infection and Immunity, vol. 81, no. 8, pp. 2686-2696. https://doi.org/10.1128/IAI.00237-13
Gbedande K, Varani S, Ibitokou AAA, Houngbegnon P, Borgella S, Nouatin O et al. Malaria modifies neonatal and early-life toll-like receptor cytokine responses. Infection and Immunity. 2013 Aug;81(8):2686-2696. https://doi.org/10.1128/IAI.00237-13
Gbedande, Komi ; Varani, Stefania ; Ibitokou, Akanni Adededji Abdoul ; Houngbegnon, Parfait ; Borgella, Sophie ; Nouatin, Odilon ; Ezinmegnon, Sem ; Adeothy, Adicatou laï ; Cottrell, Gilles ; Massougbodji, Achille ; Moutairou, Kabirou ; Troye-Blomberg, Marita ; Deloron, Philippe ; Fievet, Nadine ; Luty, Adrian J F. / Malaria modifies neonatal and early-life toll-like receptor cytokine responses. In: Infection and Immunity. 2013 ; Vol. 81, No. 8. pp. 2686-2696.
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AU - Borgella, Sophie

AU - Nouatin, Odilon

AU - Ezinmegnon, Sem

AU - Adeothy, Adicatou laï

AU - Cottrell, Gilles

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