Subversion of Cell-Autonomous Host Defense by Chlamydia Infection

Abstract

Obligate intracellular bacteria entirely depend on the metabolites of their host cell for survival and generation of progeny. Due to their lifestyle inside a eukaryotic cell and the lack of any extracellular niche, they have to perfectly adapt to compartmentalized intracellular environment of the host cell and counteract the numerous defense strategies intrinsically present in all eukaryotic cells. This so-called cell-autonomous defense is present in all cell types encountering Chlamydia infection and is in addition closely linked to the cellular innate immune defense of the mammalian host. Cell type and chlamydial species-restricted mechanisms point a long-term evolutionary adaptation that builds the basis of the currently observed host and cell-type tropism among different Chlamydia species. This review will summarize the current knowledge on the strategies pathogenic Chlamydia species have developed to subvert and overcome the multiple mechanisms by which eukaryotic cells defend themselves against intracellular pathogens.

The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion

“…As all pathogenic bacteria, Chlamydia has to subvert the host's immune system to establish a successful infection and both, the adaptive and the innate immune response are effective to control chlamydial infections (Fischer & Rudel, ). The cell autonomous immune defence present in all human cells is particularly relevant for an obligate intracellular pathogen like Chlamydia (Fischer & Rudel, ). A very efficient arm of cell autonomous defence is the removal of pathogens via autophagy.…”

A Survey of Preclinical Studies Evaluating Nanoparticle-Based Vaccines Against Non-Viral Sexually Transmitted Infections

“…trachomatis is significant to human health worldwide (Paavonen and Eggert-Kruse, 1999;Dean, 2009;World Health Organization, 2018) as it remains the most diagnosed STI in developed countries despite the availability of effective and affordable therapy. Chlamydia exists either as an extracellular elementary body (EB), which is the non-replicating, infectious form or as a reticulate body (RB), the noninfectious form that replicates intracellularly (Nans et al, 2015;Elwell et al, 2016;Fischer and Rudel, 2018). The infection is mostly asymptomatic but can induce inflammatory responses at the site of infection, causing immunopathological sequelae such as pelvic inflammatory disease (PID), ectopic pregnancy, tubal infertility, miscarriage, and trachoma (an ocular disease) (Stamm, 1999;Vasilevsky et al, 2016;Lijek et al, 2018;Murthy et al, 2018).…”

Safe haven under constant attack-TheChlamydia-containing vacuole

“…These cell‐autonomous defence strategies comprise the targeting of the pathogen to phagolysosomes or autophagosomes, interferone (IFN)‐dependent expression of cytokines and antimicrobial effectors or the activation of inflammasomes and host cell death. Chlamydia , as one of the most successful intracellular pathogens, are able to circumvent all these defence mechanisms (Finethy & Coers, ; Fischer & Rudel, ).…”

“…The deubiquitinase ChlaOTU is involved in ubiquitination clearance and thereby may protect from early autophagolysosomal degradation of the nascent inclusion (Furtado et al, ; Figure ). Thus, the highly complex interaction of Chlamydia with cell‐autonomous defence has been shaped by the coevolution of chlamydial species and their respective host as a prerequisite for intracellular adaptation (Fischer & Rudel, ).…”