Chlamydia and Its Many Ways of Escaping the Host Immune System

Figure 1

Immune evasion tactics utilized by Chlamydia sp. (a) Release of interferon γ (IFNγ) from immune cells induces expression of Indoleamine 2,3-dioxgenase (IDO) which degrades tryptophan, an essential amino acid required for Chlamydia sp. replication. IDO-mediated tryptophan depletion gives rise to bacterial stress, i.e., starvation. Under such conditions, Chlamydia sp. can produce tryptophan synthase (TrpBA) that converts indole to tryptophan. To avoid a ‘continuous’ stress situation, Chlamydia sp. enters a ‘persistence’ stage until which time the supply of tryptophan is restored. (b) Chlamydia sp. suppresses production of reactive oxygen species (ROS) and nitric oxide (NO) reducing the efficiency of phagocyte bacterial killing in phagolysosome. NADPH oxidase which is typically located on the phagolysomal membrane assists in production of bactericidal Myeloperoxidase (MPO) and hypochlorous acid (HOCl^-). In Chlamydia-infected cells, the subunit of NADPH oxidase is relocated to the inner membrane of the inclusion rather than the phagolysosome. As a consequence, Chlamydia sp. are able to survive in the phagocyte. In the neutrophil, production of chlamydial antigens such as Chlamydial-protease-like activity factor (CPAF) causes degradation of neutrophil surface formal peptide receptor inhibiting activation of neutrophils impeding neutrophil extracellular trap (NET) activity. (c) Release of CPAF from Chlamydia sp. induces expression of antiapoptotic molecule myeloid leukemia cell differentiation protein (Mcl-1) promoting degradation of proapoptotic molecules such as BCL-2-like protein 11 (Bim). Thus, Chlamydia sp. block host cell apoptosis leading to a longer period of persistence, i.e., replication within host cells. (d) CPAF degrades the major histocompatibility complex (MHC) preventing antigen presentation to T cells. Additionally, Chlamydia sp. increases PD-L1 expression in host cells. Binding of PD-L1 to the PD-1 receptor on the T cell surface constitutes a negative signal suppressing T cell receptor (TCR) activation signaling. Broken arrows denote degradation.