Table 1.
Host factors implicated in pathogenesis in murine Chlamydia infection. Comprehensive summary of in vivo Chlamydia infection models that examined inflammation and pathology. Listed are the target host factors; a brief description of the model design; the Chlamydia strain and substrain used (when available); the relevant phenotypes of the listed model and the reference for the experiments.
| Host factor | Model design | Chlamydia strain | Phenotype (compared to wt) | Citation |
|---|---|---|---|---|
| Cytokines | ||||
| IL-1 | IL1R −/− | C. muridarum (Nigg) | Increased bacterial burden, decreased pathology | Nagarajan et al. (2012) |
| IL1Ra −/− (IL-1R antagonist) | C. muridarum (Nigg) | Decreased burden, enhanced pathology | Nagarajan et al. (2012) | |
| IL1A −/− | C. muridarum (Nigg) | Decreased pathology | Gyorke et al. (2020) | |
| IL1B −/− | C. muridarum (Nigg) | Decreased pathology | Prantner et al. (2009); Gyorke et al. (2020) | |
| IL-6 | IL6 −/− | C. muridarum (Nigg clone CMG13.32.1) | Increased burden, decreased pathology | Sun et al. (2017) |
| IL-17 | IL17 −/− | C. muridarum (Weiss) | Decreased burden, decreased pathology | Andrew et al. (2013) |
| IL-12 | IL12p35 −/−, IL12p40−/− | C. muridarum (Nigg) | Increased pathology | Chen et al. (2013) |
| Type I IFN | IFNAR −/− | C. muridarum (Nigg) | Decreased burden, decreased pathology | Nagarajan et al. (2008) |
| C5 | C5 −/− | C. muridarum (Nigg) | Decreased pathology | Yang et al. (2014) |
| TNFα | TNFA −/- | C. muridarum (Nigg) | Decreased pathology | Murthy et al. (2011) |
| TNFAR1 −/- | C. muridarum (Nigg) | Decreased pathology | Dong et al. (2014) | |
| IFNγ | IFNG −/− | C. muridarum (Nigg 1942) | Increased pathology | Murthy et al. (2007); Scurlock et al. (2011) |
| Signaling molecules | ||||
| MyD88 | MyD88 −/− | C. muridarum (Nigg) | Increased uterine inflammation and hydrosalpinx | Chen et al. (2010b); Nagarajan et al. (2011) |
| STING | STING gt/gt | C. muridarum (Nigg) | Increased incidence of bilateral hydrosalpinx | Zhang et al. (2017) |
| TLR2 | TLR2 −/− | C. muridarum (Nigg) | Decreased pathology | Darville et al. (2003) |
| TLR3 | TLR3 −/− | C. muridarum (Nigg) | Increased burden, increased pathology | Carrasco et al. (2018) |
| CD28 | CD28 −/−, CD80/86−/− | C. muridarum (Nigg) | Decreased cytokine production and pathology | Chen et al. (2009) |
| CD40 | CD40 −/−, CD40L−/− | C. muridarum (Nigg) | Decreased IFNγ production, increased burden | |
| Inflammasomes | ||||
| Caspase 11 | Casp11 −/− | C. muridarum (Nigg) | Increased burden, decreased pathology | Allen et al. (2019) |
| Casp1/Casp11−/− | C. muridarum | Decreased pathology | Cheng et al. (2008) | |
| Casp1/Casp11−/− | C. trachomatis L2 | Increased fertility in infected mice | Igietseme et al. (2013) | |
| Pan-Caspase inhibitor | C. trachomatis L2 | Increased fertility in infected mice | Igietseme et al. (2013) | |
| Cell effector molecules | ||||
| MMPs | MMP chemical inhibitor | C. muridarum | Decreased ascension to upper genital tract, decreased pathology | Imtiaz et al. (2006) |
| MMP9 | MMP9 −/− | C. muridarum (Weiss) | Decreased ascension to upper genital tract, decreased pathology | Imtiaz et al. (2007) |
| iNOS (RNS) | NOS2 −/− | C. muridarum (Weiss) | Increased pathology | Ramsey et al. (2001a) |
| Phagocyte oxidase | P47phox -/− | C. muridarum (Weiss—Ramsey et al.; Nigg3 clone CMG0.1.1–Dai et al.) | Decreased pathology | Ramsey et al. (2001b); Dai et al. (2016a) |
| Perforin | Perforin −/− | C. muridarum (Nigg) | Decreased pathology | Murthy et al. (2011) |
| TAP1 | TAP1 −/− | C. muridarum (Nigg) | Decreased pathology | Murthy et al. (2011) |
| Chemokine receptors | ||||
| CXCR2 | CXCR2 −/− | C. muridarum (Weiss) | Decreased pathology | Lee et al. (2010) |
| CXCR3 | CXCR3 −/− | C. muridarum (Nigg) | Delayed bacterial clearance, decreased pathology | Jiang et al. (2017) |
| Anti-CXCR3 antibody depletion | C. trachomatis D | Decreased T cell infiltrate, decreased pathology | Xie et al. (2003) | |
| CCR7 | CCR7 −/− | C. muridarum (Weiss) | Decreased burden, decreased pathology | Li et al. (2017) |
| Cell types | ||||
| Neutrophils | Anti-GR1 antibody depletion | C. trachomatis D | Decreased neutrophil and monocyte infiltrate, decreased pathology | Lijek et al. (2018) |
| Anti-Ly6G antibody depletion | C. trachomatis D | Decreased neutrophil infiltrate, decreased pathology | Lijek et al. (2018) | |
| Mcl1-LysM-Cre (absence of mature neutrophils) | C. muridarum (03DC39) | Increased burden, decreased pathology | Zortel et al. (2018) | |
| CD8+ T cells | CD8 −/− | C. muridarum (Nigg) | Decreased pathology | Murthy et al. (2011) |
| Anti-CD8 antibody depletion | C. muridarum (Nigg—Murthy et al.) (Nigg3 clone G13.32.1–Yu et al.) | Decreased pathology | Murthy et al. (2011); Yu et al. (2019) | |
| OT-I (ovalbumin-specific CD8 T cells) | C. muridarum (Nigg) | Decreased pathology | Manam, Nicholson and Murthy (2013); Vlcek et al. (2016) | |
| CD8-derived TNFα | Adoptive transfer of TNFA−/− CD8 T cells | C. muridarum (Nigg) | Decreased pathology compared to transfer of wt CD8+ T cells | Murthy et al. (2011) |
| CD4+ T cells | Anti-CD4 antibody depletion in CD8−/− mice | C. muridarum (Nigg3 clone G13.32.1) | Decreased pathology | Yu et al. (2019) |
| Regulatory T cells | Anti-CD25 antibody depletion | C. muridarum | Decreased pathology | Moore-Connors et al. (2013) |