Faculty Collaboration Database

Immune Response to Brugia malayi Asparaginyl-tRNA Synthetase in Balb/c Mice and Human Clinical Samples of Lymphatic Filariasis. Lymphat Res Biol 2019 Aug;17(4):447-456

Date

12/21/2018

Pubmed ID

30570354

DOI

10.1089/lrb.2018.0003

Scopus ID

2-s2.0-85070831158 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Background: Lymphatic filariasis (LF) is a global health problem, with a peculiar nature of parasite-specific immunosuppression that promotes long-term pathology and disability. Immune modulation in the host by parasitic antigens is an integral part of this disease. The current study attempts to dissect the immune responses of aminoacyl-tRNA synthetases (AARS) with emphasis on Brugia malayi asparaginyl-tRNA synthetase (BmAsnRS), since it is one among the highly expressed excretory/secretory proteins expressed in all stages of the parasite life cycle, whereas its role in filarial pathology has not been elaborately studied. Methods and Results: In this study, recombinant BmAsnRS (rBmAsnRS) immunological effects were studied in semipermissive filarial animal model Balb/c mice and on clinically defined human samples for LF. In mice study, humoral responses showed considerable titer levels with IgG2a isotype followed by IgG2b and IgG1. Immunoreactivity studies with clinical samples showed significant humoral responses especially in endemic normal with marked levels of IgG1 and IgG2 followed by IgG3. The cell-mediated immune response, evaluated by splenocytes and peripheral blood mononuclear cells proliferation, did not yield significant difference when compared with control groups. Cytokine profiling and qRT-PCR analysis of mice samples immunized with rBmAsnRS showed elevated levels of IFN-γ, IL-10, inhibitory factor-cytotoxic T lymphocyte-associated protein-A (CTLA-4) and Treg cell marker-Forkhead Box P3 (FoxP3). Conclusions: These observations suggest that rBmAsnRS has immunomodulatory effects with modified Th2 response along with suppressed cellular proliferation indicating the essence of this molecule for immune evasion by the parasite.

Author List

Hameed A, Natarajan M, Jabbar S, Dhanasekaran JJ, Kumar K, Sivanesan S, Kron M, Dhanasekaran A

Author

Michael Kron MD Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, Helminth
Aspartate-tRNA Ligase
Brugia malayi
Cytokines
Disease Models, Animal
Elephantiasis, Filarial
Female
Host-Parasite Interactions
Humans
Immunoglobulin G
Leukocytes, Mononuclear
Mice
Mice, Inbred BALB C
RNA, Transfer, Amino Acyl
Recombinant Proteins
Spleen
T-Lymphocyte Subsets