Immune Responses in Lung Granulomas during Mtb/HIV Co-Infection: Implications for Pathogenesis and Therapy

Abstract

HIV and TB are the cause of significant worldwide mortality and pose a grave danger to the global public health. TB is the leading cause of death in HIV-infected persons, with one in four deaths attributable to TB. While the majority of healthy individuals infected with M. tuberculosis (Mtb) are able to control the infection, co-infection with HIV increases the risk of TB infection progressing to TB disease by over 20-fold. While antiretroviral therapy (ART), the cornerstone of HIV care, decreases the incidence of TB in HIV-uninfected people, this remains 4- to 7-fold higher after ART in HIV-co-infected individuals in TB-endemic settings, regardless of the duration of therapy. Thus, the immune control of Mtb infection in Mtb/HIV-co-infected individuals is not fully restored by ART. We do not fully understand the reasons why Mtb/HIV-co-infected individuals maintain a high susceptibility to the reactivation of LTBI, despite an effective viral control by ART. A deep understanding of the molecular mechanisms that govern HIV-induced reactivation of TB is essential to develop improved treatments and vaccines for the Mtb/HIV-co-infected population. We discuss potential strategies for the mitigation of the observed chronic immune activation in combination with both anti-TB and anti-retroviral approaches.

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

“…However, around 10% of the infected patients will develop active TB, especially in conjunction with immunodeficiency caused by malnutrition, immunosuppressive therapy using steroids, or infection with immunosuppressive pathogens 2 . Among these infection with human immunodeficiency virus (HIV) plays a pivotal role, given that immunosuppression is the hallmark of HIV pathogenesis 3 . HIV is the etiological agent for acquired immunodeficiency syndrome (AIDS), another equally important public health concern responsible for the death of over 40 million people as of 2023 4 .…”

A novel humanized mouse model for HIV and tuberculosis co-infection studies

“…However, around 10% of the infected patients will develop active TB and cause severe pathology, during primary immunodeficiency states such as defects of IL-12/IFN-g axis, lack of T and B cells in SCID mice (2), and acquired immunodeficiency caused by malnutrition, immunosuppressive therapy using steroids, or infection with immunosuppressive pathogens (3). Among these, human immunodeficiency virus (HIV) plays a pivotal role, given that CD4+ T cell depletion is the hallmark of HIV pathogenesis (4). HIV is the etiological agent for acquired immunodeficiency syndrome (AIDS), another equally important public health concern responsible for the death of over 40 million people as of 2023 (5).…”