Host cell death during infection withChlamydia: a double-edged sword

Abstract

The phylum Chlamydiae constitutes a group of obligate intracellular bacteria that infect a remarkably diverse range of host species. Some representatives are significant pathogens of clinical or veterinary importance. For instance, Chlamydia trachomatis is the leading infectious cause of blindness and the most common bacterial agent of sexually transmitted diseases. Chlamydiae are exceptionally dependent on their eukaryotic host cells as a consequence of their developmental biology. At the same time, host cell death is an integral part of the chlamydial infection cycle. It is therefore not surprising that the bacteria have evolved exquisite and versatile strategies to modulate host cell survival and death programs to their advantage. The recent introduction of tools for genetic modification of Chlamydia spp., in combination with our increasing awareness of the complexity of regulated cell death in eukaryotic cells, and in particular of its connections to cell-intrinsic immunity, has revived the interest in this virulence trait. However, recent advances also challenged long-standing assumptions and highlighted major knowledge gaps. This review summarizes current knowledge in the field and discusses possible directions for future research, which could lead us to a deeper understanding of Chlamydia’s virulence strategies and may even inspire novel therapeutic approaches.

Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis

“…The increased expression of the active phosphorylated forms p-MLKL, p-RIP1 and p-RIP3 after pathogenic infection activates the necroptotic complex necessary to initiate the membrane pore formation in those immune cells to release inflammatory arsenals (DAMPs) necessary to maintain an inflammatory milieu and thereby invite the adaptive response which results in aggravated pathogenicity ( 12 ). These biomarkers were also increased in spleen cell lysates stimulated with other pathogens ( 5 , 17 , 29 , 32 ). The spotty increased expression of those key biomarkers at 24h and 72h post infection with the nonpathogenic L. biflexa suggests a discontinuous inflammatory process as the innate response is enough to provide protection.…”

A targeted approach to investigating immune genes of an iconic Australian marsupial

“…IFNγ has a role as an immunomodulator produced by natural killer (NK) and T lymphocytes (Farrar & Schreiber, 1993). It has been shown that the presence of IFNγ in cells infected by Chlamydia can halt the developmental cycle of Chlamydia , resulting in a persistent infection (Perfettini et al, 2003; Sixt, 2021). IFNγ is required for activation of the antibody‐mediated response to Chlamydia infection (Hafner & Timms, 2018; Naglak et al, 2016).…”

“…Others played a role in lymphocyte differentiation (PATZ1), the cellular response to stress (RAD51AP1) and leukocyte migration (HSD3B7), while LAAO‐like had no GO term associations. Of the 17 genes, only three have previously been associated with disease caused by Chlamydia infection in other species (TLR5, STAT2 and IFNγ) (Beckett et al, 2012; Derbigny et al, 2005; Hosey et al, 2015; Perfettini et al, 2003; Sixt, 2021). We also identified two MHC Class I genes associated with disease progression.…”

To die or not to die: Programmed cell death responses and their interactions with Coxiella burnetii infection

“…Unsurprisingly, many intracellular bacterial species have evolved ways of inhibiting cell death signaling; nevertheless, bacterial induction of cell death during infection remains prevalent (Lamkanfi & Dixit, 2010). For instance, Chlamydia species have been shown to be capable of inhibiting host cell death during early and mid‐stages of infection and inducing death at later stages, allowing for pathogen dissemination (Sixt, 2021). Chlamydia can also induce death in neighboring cells, which may prevent activation of an immune response by depleting immune cells (Sixt, 2021).…”

“…For instance, Chlamydia species have been shown to be capable of inhibiting host cell death during early and mid‐stages of infection and inducing death at later stages, allowing for pathogen dissemination (Sixt, 2021). Chlamydia can also induce death in neighboring cells, which may prevent activation of an immune response by depleting immune cells (Sixt, 2021). With regard to C. burnetii , apoptosis plays an important role in infection, as do autophagy and pyroptosis (Cordsmeier et al, 2019).…”