Innate immunity in tuberculosis: host defense vs pathogen evasion

Abstract

The major innate immune cell types involved in tuberculosis (TB) infection are macrophages, dendritic cells (DCs), neutrophils and natural killer (NK) cells. These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis (Mtb) through various pattern recognition receptors (PRRs), including but not limited to Toll-like receptors (TLRs), Nod-like receptors (NLRs) and C-type lectin receptors (CLRs). Upon infection by Mtb, the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis, autophagy, apoptosis and inflammasome activation. In contrast, Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity. Here we discuss recent research on major host innate immune cells, PRR signaling, and the cellular functions involved in Mtb infection, with a specific focus on the host's innate immune defense and Mtb immune evasion. A better understanding of the molecular mechanisms underlying host-pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.

Figure 1

Major host immune cells, pattern recognition receptors and cellular functions involved in innate immune defense against Mtb. Mtb mainly infects innate immune cells, including macrophages, dendritic cells, neutrophils and natural killer cells. Those immune cells recognize Mtb through various pattern recognition receptors, including Toll-like receptors (such as TLR1, TLR2, TLR4, TLR7, TLR8 and TLR9), Nod-like receptors (such as NOD1, NOD2, NLRP3 and NLRC4) and C-type lectin receptors (such as MR, DC-SIGN, Mincle, Dectin-1 and Dectin-2, Dectin-3, CL-LK and DCIR). During Mtb infection, the host orchestrates signaling from those PRRs and launches a variety of cellular functions, such as phagocytosis, autophagy, apoptosis and inflammasome activation, to control or eliminate Mtb.

Figure 2

Mtb components interfering with host cellular functions. During Mtb infection, multiple Mtb components interfere (either activate or inhibit) with host cellular functions (such as phagocytosis, autophagy, apoptosis and inflammasome activation) to help the pathogen evade or circumvent host innate immunity. For example, PPE57 promotes phagocytosis, whereas PIMs, ManLAM, PknG, PtpA and EIS inhibit the complete phagocytosis of macrophages through arresting phagosome maturation; ESAT-6 and C-di-AMP activate, whereas EIS, SapM, LrpG and PDIM inhibit autophagy. Many Mtb components can either activate (including LpqH, PE_PGRS33, ESAT-6, OppD, PstS1, Rv0183, Rv0901, PE9/PE10 and Mce4A) or inhibit (including PtpA, NuoG, PknE, SecA2, SodA, SigH, MPT64 and Rv3354) apoptosis; EsxA and Mtb DNA can activate, whereas Zmp1 can inhibit inflammasome activation.