Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection

Marina Nosik; Maria G Belikova; Konstantin Ryzhov; Darya Avdoshina; Alexandr Sobkin; Vitaly Zverev; Oxana Svitich

doi:10.3390/v15061330

Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection

Viruses. 2023 Jun 6;15(6):1330. doi: 10.3390/v15061330.

Authors

Marina Nosik¹, Maria G Belikova^{2

3

4}, Konstantin Ryzhov¹, Darya Avdoshina³, Alexandr Sobkin⁵, Vitaly Zverev¹, Oxana Svitich¹

Affiliations

¹ I.I. Mechnikov Institute of Vaccine and Sera, 105064 Moscow, Russia.
² N.F. Gamaleya National Research Center for Epidemiology and Microbiology, 123098 Moscow, Russia.
³ Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences, 108819 Moscow, Russia.
⁴ Translational Medicine Cluster, Peoples' Friendship University of Russia, 117198 Moscow, Russia.
⁵ Department for Treatment of TB Patients with HIV Infection, G.A. Zaharyan Moscow Tuberculosis Clinic, 125466 Moscow, Russia.

Abstract

HIV-1 infection is characterized by aberrant immune activation, and infection with M. tuberculosis by an unbalanced production of proinflammatory cytokines. The expression of these cytokines in HIV-1/TB coinfection is still understudied. Here, we aimed to compare the production of proinflammatory cytokines in drug-naive patients coinfected with HIV-1 and M. tuberculosis (HIV/TB) compared to patients with respective monoinfections. Plasma samples of patients with HIV/TB coinfection (n = 36), HIV-1 monoinfection (n = 36), and TB monoinfection (n = 35) and healthy donors (n = 36) were examined for the levels of eight proinflammatory cytokines. Their levels were significantly increased in all patient groups compared to healthy donors. At the same time, a drastic decrease in the plasma levels of IFN-γ, TNF-α, Il-1β, IL-15, and IL-17 was detected in patients with HIV/TB coinfection compared to patients with HIV-1 or TB monoinfections. The plasma levels of IL-17 characterized the TB severity: in HIV/TB-coinfected patients with disseminated TB, plasma levels of IL-17 were eight times lower than in patients with less severe TB forms (infiltrative TB or TB of intrathoracic lymph nodes; p < 0.0001). At the same time, HIV/TB-coinfected patients had increased plasma levels of IL-8, IL-12, and IL-18, with the levels of IL-8 correlating with mortality (p < 0.0001). Thus, on the contrary to the patients with HIV-1 or TB monoinfections, HIV/TB-coinfected patients had suppressed production of most of the proinflammatory cytokines associated with antimicrobial immune response, specifically of T-cells involved in the containment of both infections. At the same time, they demonstrated an expansion of proinflammatory cytokines known to originate from both hematopoietic and nonhematopoietic cells, and manifest tissue inflammation. In HIV-1/TB coinfection, this leads to the disruption of granuloma formation, contributing to bacterial dissemination and enhancing morbidity and mortality.

Keywords: HIV-infection; HIV/TB coinfection; proinflammatory cytokines; treatment-naïve; tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Coinfection*
Cytokines / metabolism
HIV Infections*
HIV Seropositivity*
HIV-1*
Humans
Interleukin-17
Interleukin-8
Mycobacterium tuberculosis*
Tuberculosis* / complications

Substances

Cytokines
Interleukin-17
Interleukin-8

Grants and funding

The study was carried out with the Collective Usage Center “I.I. Mechnikov NIIVS”, Moscow, Russia. M.G.B. was supported by the Translational Medicine Cluster, Peoples’ Friendship University of Russia, and N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Moscow, Russia.