title: Toll like receptors in self-recovering hepatitis E patients with or without pregnancy.
abstract: Hepatitis E virus (HEV) causes high mortality among pregnant women. Pathogenesis of HEV, especially during pregnancy, is poorly understood. Our aim was to assess the role of Toll-like-receptors (TLRs) in hepatitis E patients with pregnancy (Antenatal care, ANC) or without pregnancy (non-ANC). The patient categories included acute-phase, non-ANC (n=46) and ANC patients (2nd/3rd trimesters, n=13) and non-ANC patients (n=31) during convalescence. Controls included apparently healthy non-ANC (n=30) and ANC subjects in the first (n=10) and later (2nd/3rd, n=20) trimesters. TLR2/TLR3/TLR4/TLR7/TLR8 levels were determined by flow-cytometry. Cytokine responses induced by TLR-specific-ligands-stimulated-PBMCs from ANC/non-ANC-patients and TLR-signaling-molecules (non-ANC-patients) were measured. PBMCs were used to assess gene expression levels by TaqMan-Low-Density-Array. Compared to the temporal activation of TLR4/TLR7/TLR8 at protein and mRNA levels, the ANC-patients and controls exhibited reduced TLRs indicative of impaired TLR response. Stimulation of PBMCs with TLR-specific ligands led to the induction of type-I interferons, IFNβ by the non-ANC group and IFNα by the ANC category. Involvement of MyD88-independent (TLR3/TLR4) and MyD88-dependent (TLR4/TLR7/TLR8) pathways and association of TLR4/TLR7/TLR8 with recovery was documented in the non-ANC-patients. Except for robust type-I-interferon response, HEV infection could not modulate pregnancy-related diminished immune response. The results have implications in the understanding of HEV pathogenesis.
authors.affiliation: Hepatitis Group, National Institute of Virology, Pune, India.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Arya
authors.affiliation: Hepatitis Group, National Institute of Virology, Pune, India. Electronic address: varankalle@yahoo.com.
authors.forename: Vidya A
authors.initials: VA
authors.lastname: Arankalle
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D016751:Hepatitis E / Q000276:immunology*; D016752:Hepatitis E virus / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000097:blood* / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D016899:Interferon-beta; D007371:Interferon-gamma
keywords: Hepatitis E; MyD-dependent pathway; Pregnancy; TRIF mediated pathway; Toll like receptors