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

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

doi:10.3389/fmicb.2020.01685

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.

Highlights

Galectin-9 (Gal-9) and osteopontin (OPN) are matricellular proteins (MCPs) which play an important role in inflammation and tissue remodeling by acting as connective tissue growth factors
There was no significant difference in HIV−pulmonary tuberculosis (PTB)+ and extrapulmonary tuberculosis (EPTB)+ patients
Gal-9 and OPN having immunomodulatory functions act as immune check inhibitors and play an important role in many infectious as well as non-infectious diseases

Summary

INTRODUCTION

Galectin-9 (Gal-9) and osteopontin (OPN) are matricellular proteins (MCPs) which play an important role in inflammation and tissue remodeling by acting as connective tissue growth factors. OPN was shown to tip the balance of myeloid and lymphoid populations in mice (Kanayama et al, 2017) and was found to be positively associated with neutrophils numbers and negatively with lymphocyte numbers in TB patients (Shiratori et al, 2016) These findings point to the need to evaluate immunopathogenic roles of OPN and Gal-9 in HIV/TB co-infections. Since HIV infected patients are likely to present with sputum negative PTB or EPTB (Swaminathan et al, 2010; Rosso et al, 2011), their diagnosis is always challenging We evaluated these proteins to determine if they can be used as biomarkers indicating development of active tuberculosis in HIV infection

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT