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

摘要

Graphical depiction of the mycobacterial set point as a theoretical construct, represented as the Mycobacterium tuberculosis (Mtb) bacterial burden after infection, either alone or in the context of HIV coinfection. After infection, Mtb bacterial burden increases until adaptive immunity is activated, thereby establishing the mycobacterial set point. Alveolar macrophages, the first cells to encounter Mtb, are an important component of the early innate immune response to Mtb. As reviewed in the main text, the mycobacterial burden at the point of adaptive immune activation plays a important role in the subsequent control of infection and progression to active tuberculosis disease. In the case of HIV coinfection, impairments in alveolar macrophage functions lead to poor early immune control of Mtb which, in turn, leads to a higher mycobacterial set point and greater Mtb bacterial burden at the time when adaptive immunity is activated