Toll like receptors in self-recovering hepatitis E patients with or without pregnancy

• Published in: Human immunology Vol. 75; no. 12; pp. 1147 - 1154
• Main Authors: Arya, Ravi P., Arankalle, Vidya A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014
• Subjects: Allergy and Immunology; Cells, Cultured; Cytokines - immunology; Female; Hepatitis E; Hepatitis E - immunology; Hepatitis E virus - immunology; Humans; Interferon-beta - biosynthesis; Interferon-beta - immunology; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; MyD-dependent pathway; Myeloid Differentiation Factor 88 - immunology; Pregnancy; Pregnancy Complications, Infectious; Signal Transduction - immunology; Toll like receptors; Toll-Like Receptors - blood; Toll-Like Receptors - genetics; Toll-Like Receptors - immunology; TRIF mediated pathway; Hepatitis E; IL; poly I:C; Toll like receptors; NFkB; R848; TNF; LPS; IFN; Pregnancy; IRAK; IkBα; TBK1; ANC; TRIF mediated pathway; MyD-dependent pathway; HEV; TLR; IRF; polyinosinic:polycytidylic acid; hepatitis E virus; Antenatal care (pregnancy); TANK-binding kinase 1; interleukin; nuclear factor kappa-light-chain-enhancer of activated B cells; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; interferon regulatory transcription factor; interleukin-1 receptor-associated kinase; TLR7/8-ligand; interferon; tumor necrosis factor; lipopolysaccharide
• ISSN: 0198-8859; 1879-1166; 1879-1166
• DOI: 10.1016/j.humimm.2014.10.011

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.