Immune Response to Brugia malayi Asparaginyl-tRNA Synthetase in Balb/c Mice and Human Clinical Samples of Lymphatic Filariasis.

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.

• Authors: Afaq Hameed, Mahalakshmi Natarajan, Salih Jabbar, Jeeva Jothi Dhanasekaran, Krishna Kumar, Sanjana Sivanesan, Michael Kron, Anuradha Dhanasekaran
• Journal: Lymphatic research and biology (Lymphat Res Biol) Vol. 17 Issue 4 Pg. 447-456 (08 2019) ISSN: 1557-8585 [Electronic] United States
• PMID: 30570354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Helminth
• Cytokines
• Immunoglobulin G
• RNA, Transfer, Amino Acyl
• Recombinant Proteins
• Aspartate-tRNA Ligase
• asparaginyl-tRNA synthetase

Topics

• Animals
• Antigens, Helminth (immunology)
• Aspartate-tRNA Ligase (genetics, immunology, isolation & purification)
• Brugia malayi (enzymology, immunology)
• Cytokines (metabolism)
• Disease Models, Animal
• Elephantiasis, Filarial (diagnosis, immunology, parasitology)
• Female
• Host-Parasite Interactions (immunology)
• Humans
• Immunoglobulin G (immunology)
• Leukocytes, Mononuclear (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• RNA, Transfer, Amino Acyl (genetics, immunology, isolation & purification)
• Recombinant Proteins
• Spleen (cytology, immunology)
• T-Lymphocyte Subsets (immunology, metabolism)