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Your search keyword '"Rashmi Govind Virkar"' showing total 2 results
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2 results on '"Rashmi Govind Virkar"'

1. HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load

Author

Srabanti Rakshit, Nitin Hingankar, Shuba Varshini Alampalli, Vasista Adiga, Bharath K. Sundararaj, Pravat Nalini Sahoo, Greg Finak, Anto Jesuraj Uday Kumar J, Chirag Dhar, George D’Souza, Rashmi Govind Virkar, Manisha Ghate, Madhuri R. Thakar, Ramesh S. Paranjape, Stephen C. De Rosa, Tom H.M. Ottenhoff, and Annapurna Vyakarnam

Subjects
HIV, tuberculosis, CD4+ T cells, CD8+ T cells, Th17, ART, Biology (General), QH301-705.5
Abstract

Summary: HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis (Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4+ T cell responses demonstrates a marked dampening of the Mtb-specific CD4+ T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ+/interleukin-17+ (IL-17+) and significant loss of anti-inflammatory IL-10+/IL-17+ effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4+ T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4+ T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects.

Published
2020
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2. Elevated Levels of Galectin-9 but Not Osteopontin in HIV and Tuberculosis Infections Indicate Their Roles in Detecting MTB Infection in HIV Infected Individuals

Author

Gaowa Bai, Sandip Patil, Annapurna Vyakarnam, Vishwanath Pujari, Rashmi Govind Virkar, Shubhangi Bichare, Toshio Hattori, Madhuri Thakar, Raman R. Gangakhedkar, Toshiro Niki, Ashwini Shete, and Manisha Ghate

Subjects
Microbiology (medical), Tuberculosis, osteopontin, Human immunodeficiency virus (HIV), lcsh:QR1-502, Disease, medicine.disease_cause, Microbiology, lcsh:Microbiology, Pathogenesis, galectin-9, 03 medical and health sciences, medicine, latent tuberculosis, Osteopontin, extrapulmonary tuberculosis, Original Research, 030304 developmental biology, Galectin, HIV/tuberculosis co-infection, 0303 health sciences, Latent tuberculosis, biology, 030306 microbiology, business.industry, HIV, medicine.disease, Immunology, biology.protein, business, Viral load, pulmonary tuberculosis
Abstract

Galectin-9 (Gal-9) and osteopontin (OPN) play immunomodulatory roles in tuberculosis and HIV infections. Evaluation of their levels as well as their interplay with different pro-inflammatory cytokines is critical to understand their role in immunopathogenesis of HIV/tuberculosis co-infection considering the complexity of the disease. Plasma levels of these proteins were measured by ELISAs in HIV-negative individuals with pulmonary (n = 21), extrapulmonary (n = 33), and latent tuberculosis (n = 22) and in HIV infected patients with pulmonary (n = 14), latent tuberculosis (n = 17), and without tuberculosis (n = 41). Levels of pro-inflammatory cytokines were estimated by Luminex assay. Receiver operated characteristic curve analysis was performed to evaluate discriminatory roles of these proteins. Spearman’s correlation analysis was performed with the markers of HIV and tuberculosis disease progression to evaluate their immunopathogenic roles. Gal-9 and OPN levels were higher in HIV uninfected patients with active tuberculosis than with latent tuberculosis. Gal-9 but not OPN levels were higher in HIV infected patients with active tuberculosis than with latent tuberculosis. Area under curve for Galectin-9 was >0.9 in HIV/tuberculosis co-infection and extrapulmonary tuberculosis. OPN and IL-6 levels were higher in patients with severe chest X-ray grade indicating its association with severity of the disease and positively correlated with each other. Stronger positive and negative correlations of Gal-9 levels, respectively, with viral loads and CD4 cell counts in HIV infected patients were observed than OPN levels indicating their association with HIV disease progression. Thus, significantly elevated Gal-9 levels were reported for the first time in HIV/tuberculosis co-infection and extrapulmonary tuberculosis in our study than single infections with HIV and tuberculosis. The study indicated a need for further evaluation of monitoring role of Gal-9 for detection of developing tuberculosis in HIV infected individuals. The findings also indicated differential roles of Gal-9 and OPN in the pathogenesis of tuberculosis and HIV infections.

Published
2020
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