Toll-Like Receptors 2 and 4, Nitric Oxide, and Myeloid Differentiation Primary Response 88 in Women Infected with Toxoplasma Gondii
Abstract
Background: The host resistance to Toxoplasma gondii is initiated by innate recognition of Toll-like receptors (TLRs), which reach the adaptor myeloid differentiation primary response 88 (MyD88) to drive interferon-γ (IFN-y)-dependent nitric oxide (NO) production. Human studies of the integration of these mediators in reproductive-age women are extremely scarce. Objectives: To quantify plasma TLR-2, TLR-4, MyD88, NO and IFN-γ in women infected with T. gondii compared to seronegative controls, to relate TLR-2/TLR-4 activity to the leukocyte response, and to study the MyD88 L265P variant. Materials and methods: 150 women of reproductive age were screened, and the 96 with ELISA-confirmed T. gondii infection formed the case group, compared with 50 age-matched seronegative controls (18-50 years) in a case-control study. Infection was established by latex agglutination, IgG/IgM ELISA and amplification of the parasite B1 gene. Plasma mediators were measured using sandwich ELISA and MyD88 L265P was screened by PCR-RFLP (BsiEI). Groups were compared using Student t or Mann-Whitney U test (p < 0.05). Results: Latex agglutination was positive in 111 of 150 screened women (74%); ELISA confirmed infection in 96 of these, of whom 81.25% were IgG-positive (chronic) and 18.75% IgM-positive (recent), while all controls were negative. Infected women had neutrophil-skewed leukocytosis with less haemoglobin. TLR-2, TLR-4, MyD88, NO and IFN-γ were all significantly elevated (p < 0.04) with IFN-γ having the largest fold-change (≈5.5×). The MyD88 L265P variant was detected in only one of 4 sequenced cases. Conclusion: This coordinated up-regulation of the TLR-MyD88-NO axis highlights the peripheral immune response to T. gondii in women and is a potential biomarker panel and target for immunomodulatory activity. The MyD88 L265P observation is preliminary and we would like to confirm this in larger cohorts.