The innate immune response in human tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini-review, we discuss these host-pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome-wide association studies).

Figure 1

Cells involved in the human innate immune response to tuberculosis. Upon inhalation into the lung, Mtb (black rod) travels along the trachea, bronchus and bronchioles to the alveoli. Lining the airway is the respiratory mucosa (A). This consists of a layer of AECs that provide a tight barrier to prevent Mtb from invading the tissue and they have many receptors to detect Mtb. AECs control the composition of ASL, a substance containing mucus, anti‐microbial peptides, antibodies and cytokines/chemokines. The lamina propria supports the epithelium and also contains immune cells such as macrophages and MAIT that respond to infection. Mtb eventually reach the alveolae (B), which are surrounded by a network of capillaries to facilitate gas exchange. The alveolus (C) is structurally formed from type I epithelial cells, and type II epithelial cells are often found at the cell junctions. Type II cells secrete a variety of anti‐microbial substances including pulmonary surfactant. AMs and DCs are the primary resident defenders of the alveolus. They are effective phagocytes and have a range of intrinsic anti‐microbial capacities. In addition, neutrophils and NKs are recruited from the surrounding capillaries to bolster the host defence. Cells are not drawn to scale.