HIV and the tuberculosis “set point”: how HIV impairs alveolar macrophage responses to tuberculosis and sets the stage for progressive disease

Abstract

As HIV has fueled a global resurgence of tuberculosis over the last several decades, there is a growing awareness that HIV-mediated impairments in both innate and adaptive immunity contribute to the heightened risk of tuberculosis in people with HIV. Since early immune responses to Mycobacterium tuberculosis (Mtb) set the stage for subsequent control or progression to active tuberculosis disease, early host–pathogen interactions following Mtb infection can be thought of as establishing a mycobacterial “set point,” which we define as the mycobacterial burden at the point of adaptive immune activation. This early immune response is impaired in the context of HIV coinfection, allowing for a higher mycobacterial set point and greater likelihood of progression to active disease with greater bacterial burden. Alveolar macrophages, as the first cells to encounter Mtb in the lungs, play a critical role in containing Mtb growth and establishing the mycobacterial set point. However, a number of key macrophage functions, ranging from pathogen recognition and uptake to phagocytosis and microbial killing, are blunted in HIV coinfection. To date, research evaluating the effects of HIV on the alveolar macrophage response to Mtb has been relatively limited, particularly with regard to the critical early events that help to dictate the mycobacterial set point. A greater understanding of alveolar macrophage functions impacted by HIV coinfection will improve our understanding of protective immunity to Mtb and may reveal novel pathways amenable to intervention to improve both early immune control of Mtb and clinical outcomes for the millions of people worldwide infected with HIV.

Expression of MicroRNAs Is Dysregulated by HIV While Mycobacterium tuberculosis Drives Alterations of Small Nucleolar RNAs in HIV Positive Adults With Active Tuberculosis

“…Thus, it is tempting to speculate that these alterations may directly be involved in the insufficient TB control in PWH, since miRNAs reportedly play an important role in multiple immunological responses ( Drury et al, 2017 ). Macrophages play a key role in the interactions between HIV and Mtb ( Auld and Staitieh, 2020 ), as both pathogens infect these cells ( Gartner, 2014 ; Esmail et al, 2018 ). Moreover, HIV-infected macrophages show increased Mtb growth ( Pathak et al, 2010 ), impaired phagocytosis ( Mazzolini et al, 2010 ), and reduced phagosomal proteolysis function ( Jambo et al, 2014 ).…”

Improved Algorithm-Based Magnetic Resonance Images Combined with Computed Tomography in the Diagnosis of Acquired Immune Deficiency Syndrome Combined with Spinal Tuberculosis

“…e death rate of AIDS combined with spinal tuberculosis is as high as 80%. erefore, the accurate diagnosis and examination of the disease are extremely important [25,26]. In this study, an improved algorithm was proposed based on MRI combined with CT to diagnose and check AIDS combined with spinal tuberculosis.…”

Early innate cell interactions with Mycobacterium tuberculosis in protection and pathology of tuberculosis

“…As mentioned earlier, alveolar macrophages (AM) play a crucial role in interacting with Mtb and initiating innate immune responses in the lungs. In HIV patients, these AM act as reservoirs for the virus, significantly impairing their phagocytic killing capacity and cytokine production ( 245 , 246 ). Consequently, these AM become more susceptible to Mtb infections and are unable to carry out their anti-mycobacterial functions effectively ( 247 ).…”

“…Furthermore, HIV-Mtb coinfection leads to an increase in the production of proinflammatory cytokines, such as IL-1β, IL-6, and GM-CSF, supporting enhanced viral replication ( 251 , 252 ). Consequently, the coinfection of HIV and Mtb in AM results in a synergistic effect characterized by impaired cell phagocytosis, a shift towards necrosis over apoptosis, and increased production of proinflammatory cytokines, ultimately promoting the proliferation of both pathogens ( 246 ).…”