Chlamydia muridarumInfection of Macrophages Stimulates IL-1βSecretion and Cell Death via Activation of Caspase-1 in an RIP3-Independent Manner

Abstract

Chlamydiae are Gram-negative bacteria, which replicate exclusively in the infected host cells. Infection of the host cells by Chlamydiae stimulates the innate immune system leading to an inflammatory response, which is manifested not only by secretion of proinflammatory cytokines such as IL-1β from monocytes, macrophages, and dendritic cells, but also possibly by cell death mediated by Caspase-1 pyroptosis. RIP3 is a molecular switch that determines the development of necrosis or inflammation. However, the involvement of RIP3 in inflammasome activation by Chlamydia muridarum infection has not been clarified. Here, we assessed the role of RIP3 in synergy with Caspase-1 in the induction of IL-1β production in BMDM after either LPS/ATP or Chlamydia muridarum stimulation. The possibility of pyroptosis and necroptosis interplays and the role of RIP3 in IL-1β production during Chlamydia muridarum infection in BMDM was investigated as well. The data indicated that RIP3 is involved in NLRP3 inflammasome activation in LPS/ATP-stimulated BMDMs but not in Chlamydia muridarum infection. Pyroptosis occurred in BMDM after LPS/ATP stimulation or Chlamydia muridarum infection. Moreover, the results also illuminated the important role of the Caspase-1-mediated pyroptosis process which does not involve RIP3. Taken together, these observations may help shed new light on details in inflammatory signaling pathways activated by Chlamydia muridarum infection.

Bifidobacterium animalis ssp. Lactis 420 Mitigates Autoimmune Hepatitis Through Regulating Intestinal Barrier and Liver Immune Cells

“…Previous studies have already shown that LPS induced programmed cell death and thereby increased the expressions of its target genes, such as RIP3 and MLKL ( 77 , 78 ). Recent studies demonstrated that some harmful pathogen also activated RIP3 signaling pathway including Staphylococcus aureus , Chlamydia muridarum and influenza H7N9 virus ( 79 – 81 ). In our study, mice in EAH group showed elevated serum LPS level and increased abundance of pathogenic bacteria including Bacteroides and Ruminococcus.…”

Chlamydia Lipooligosaccharide Has Varied Direct and Indirect Roles in Evading both Innate and Adaptive Host Immune Responses

“…Recent reports have suggested that chlamydial infections can trigger a second programmed cell death pathway, pyroptosis, if cells have functional inflammasomes (55,56), particularly the noncanonical inflammasome (57). LPS can interact directly with noncanonical inflammasomes to trigger pyroptosis (40)(41)(42); however, transfection of chlamydial LOS into macrophages failed to induce pyroptosis (52).…”

Clear Victory for Chlamydia: The Subversion of Host Innate Immunity

“…can also infect and initiate apoptosis in immune cells such as macrophages and neutrophils. For example, on C. trachomatis infection, macrophages and neighboring T cells become susceptible to apoptosis in a caspase-1- (Chen et al, 2017) and TNF-α-dependent manner (Jendro et al, 2004), respectively. C. pneumoniae also inhibits the proliferation of activated T cells via the initiation of apoptotic pathways (Olivares-Zavaleta et al, 2011).…”

“…Meanwhile, the TW-183, AR-39, and TWAR strains of C. pneumoniae are the most likely to target human Mono Mac 6 cells, murine alveolar macrophages, and bone-marrow-derived macrophages (BMDMs), respectively (Beagley et al, 2009). Although it is clear that macrophages are not the optimum host cell targets for Chlamydia , owing to their powerful ability to engulf and destroy bacteria, chlamydial persistence following the infection of macrophages can be achieved through (1) the formation of aberrant RBs, to overcome imperfect conditions for growth; (2) the interaction with multiple cytoskeletons, the Golgi, and the endoplasmic reticulum, to acquire sufficient nutrients (Paradkar et al, 2008; Sun et al, 2012; Elwell et al, 2016); (3) the up- or downregulation of inflammatory mediators such as TNF-α, IFN-γ, and ILs, to escape eradication by interfering with apoptotic and autophagic pathways (Jendro et al, 2004; Sherchand et al, 2016; Chen et al, 2017); and (4) the production of adhesion molecules such as the intercellular cell adhesion molecule-1 (ICAM-1), to increase macrophage adherence, thus facilitating the migration of EBs to their preferred sites of replication (Yeung et al, 2017). The persistence of the Chlamydia spp.…”