Maternal<i>Trypanosoma cruzi</i>Infection Upregulates Capacity of Uninfected Neonate Cells To Produce Pro- and Anti-Inflammatory Cytokines

Vekemans, Johan; Truyens, Carine; Torrico, Faustino; Solano, Marco; Torrico, Mary-Cruz; Rodríguez, Patricia; Alonso-Vega, Cristina; Carlier, Yves

doi:10.1128/iai.68.9.5430-5434.2000

Cited by 67 publications

(62 citation statements)

References 43 publications

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“…The ability of this protozoan parasite to stimulate the synthesis of proinflammatory cytokines has also been shown in humans PBMCs (50,51). In addition, high levels of TNF-␣ and IFN-␥ are produced in the site of infection, as observed in the heart tissue from patients with chronic ChagasЈ disease (52,53).…”

Section: The Myd88mentioning

confidence: 97%

Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection withTrypanosoma cruziin Mice Lacking Functional Myeloid Differentiation Factor 88

Campos

Closel

Valente³

et al. 2004

The Journal of Immunology

160

192

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Studies performed in vitro suggest that activation of Toll-like receptors (TLRs) by parasite-derived molecules may initiate inflammatory responses and host innate defense mechanisms against Trypanosoma cruzi. Here, we evaluated the impact of TLR2 and myeloid differentiation factor 88 (MyD88) deficiencies in host resistance to infection with T. cruzi. Our results show that macrophages derived from TLR2 −/− and MyD88−/− mice are less responsive to GPI-mucin derived from T. cruzi trypomastigotes and parasites. In contrast, the same cells from TLR2−/− still produce TNF-α, IL-12, and reactive nitrogen intermediates (RNI) upon exposure to live T. cruzi trypomastigotes. Consistently, we show that TLR2−/− mice mount a robust proinflammatory cytokine response as well as RNI production during the acute phase of infection with T. cruzi parasites. Further, deletion of the functional TLR2 gene had no major impact on parasitemia nor on mortality. In contrast, the MyD88−/− mice had a diminished cytokine response and RNI production upon acute infection with T. cruzi. More importantly, we show that MyD88−/− mice are more susceptible to infection with T. cruzi as indicated by the higher parasitemia and accelerated mortality, as compared with the wild-type mice. Together, our results indicate that T. cruzi parasites elicit an alternative inflammatory pathway independent of TLR2. This pathway is partially dependent on MyD88 and necessary for mounting optimal inflammatory and RNI responses that control T. cruzi replication during the early stages of infection.

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Section: The Myd88mentioning

confidence: 97%

Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection withTrypanosoma cruziin Mice Lacking Functional Myeloid Differentiation Factor 88

Campos

Closel

Valente³

et al. 2004

The Journal of Immunology

160

192

View full text Add to dashboard Cite

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“…Maternal infection with Trypanosoma cruzi, for example, without vertical transmission, stimulates fetal innate and adaptive immune responses such that exposed but uninfected neonates produce higher concentrations of proinflammatory and anti-inflammatory cytokines than their unexposed counterparts (3,4). Maternal infection with Schistosoma spp.…”

mentioning

confidence: 99%

Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses

et al. 2013

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g 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. TLRmediated interleukin 6 (IL-6) and IL-10 production was robust at birth and then stabilized, whereas tumor necrosis factor alpha (TNF-␣) and gamma interferon (IFN-␥) 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-␣ 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 TLRmediated 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.

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“…There is increasing evidence that T. cruzi infection in pregnant women can induce the activation of T lymphocytes of the fetus in utero (11)(12)(13). Although the production of proinflammatory cytokines like IL-1b, IL-6, and TNF-a in response to T. cruzi Ags and the spontaneous release of TNF-a in uninfected infants born to T. cruzi-infected mothers (B 2 M + ) have been described, the levels of these cytokines in congenitally infected newborns are rather low (11,(13)(14)(15)(16), suggesting that the immune response might be an important factor in vertical transmission (17).…”

mentioning

confidence: 99%

Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure

Volta

Bustos

Cardoni

et al. 2016

The Journal of Immunology

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Trypanosoma cruzi, the causing agent of Chagas disease, leads to an activation of the immune system in congenitally infected infants. In this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative PCR in the circulation of neonates born to T. cruzi–infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. We conducted a retrospective cohort study of 35 infants with congenital T. cruzi infection, of which 15 and 10 infants had been diagnosed by detection of parasites by microscopy in the first and sixth month after delivery, respectively, and the remaining 10 had been diagnosed by the presence of T. cruzi–specific Abs at 10–12 mo old. Uninfected infants born to either T. cruzi–infected or uninfected mothers were also evaluated as controls. The plasma levels of IL-17A, MCP-1, and monokine induced by IFN-γ were increased in infants congenitally infected with T. cruzi, even before they developed detectable parasitemia or seroconversion. Infants diagnosed between 6 and 12 mo old also showed increased levels of IL-6 and IL-17F at 1 mo of age. Conversely, infants who did not develop congenital T. cruzi infection had higher levels of IFN-γ than infected infants born to uninfected mothers. Monokine induced by IFN-γ, MCP-1, and IFN-γ production induced in T. cruzi–infected infants correlated with parasitemia, whereas the plasma levels of IL-17A, IL-17F, and IL-6 were less parasite load dependent. These findings support the existence of a distinct profile of cytokines and chemokines in the circulation of infants born to T. cruzi–infected mothers, which might predict congenital infection.

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MaternalTrypanosoma cruziInfection Upregulates Capacity of Uninfected Neonate Cells To Produce Pro- and Anti-Inflammatory Cytokines

Cited by 67 publications

References 43 publications

Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection withTrypanosoma cruziin Mice Lacking Functional Myeloid Differentiation Factor 88

Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection withTrypanosoma cruziin Mice Lacking Functional Myeloid Differentiation Factor 88

Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses

Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure

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