<i>Chlamydia trachomatis</i> vacuole maturation in infected macrophages

Sun, He; Eng, Edward W.; Jeganathan, Sujeeve; Sin, Alex T.-W.; Patel, Prerna C.; Gracey, Eric; Inman, Robert D.; Terebiznik, Mauricio R.; Harrison, Rene E.

doi:10.1189/jlb.0711336

Cited by 40 publications

(43 citation statements)

References 50 publications

(58 reference statements)

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“…Material that reacted with Chla- Fields et al mydia-specific antibodies was routinely detected in dispersed, punctate patterns in control BV2 cells, whereas mature inclusions were rarely observed. This pattern is consistent with a previous report indicating killing of chlamydiae in macrophages via autophagy (12). In contrast, treatment of cells with perforin-2 siRNA resulted in the routine detection of apparently intact, mature chlamydial inclusions.…”

Section: Resultssupporting

confidence: 81%

“…Multiple reports have documented the ability of professional phagocytes to directly kill intracellular chlamydiae (12,14,18). Given the constitutive expression of Mpeg1/perforin-2 in macrophages (15) and the role of perforin-2 in limiting intracellular bacterial replication (17), we questioned whether perforin-2 might contribute to the limitation of chlamydial growth in macrophages.…”

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confidence: 99%

“…C. trachomatis infection of macrophages yields only 2 to 3% of the progeny detected in comparative epithelial infections. A majority of chlamydiae are rapidly targeted to Rab7-positive lysosomal compartments and do not incorporate viability biomarkers (12). Macrophage-dependent destruction of C. trachomatis has been associated with host cell autophagy (12)(13)(14), and treatment of macrophages with autophagy-inhibiting drugs such as bafilomycin A1 results in a modest increase in chlamydial growth (13,14).…”

mentioning

confidence: 99%

“…A majority of chlamydiae are rapidly targeted to Rab7-positive lysosomal compartments and do not incorporate viability biomarkers (12). Macrophage-dependent destruction of C. trachomatis has been associated with host cell autophagy (12)(13)(14), and treatment of macrophages with autophagy-inhibiting drugs such as bafilomycin A1 results in a modest increase in chlamydial growth (13,14). Furthermore, autophagy-dependent killing of chlamydiae is enhanced after treatment with gamma interferon (IFN-␥) and requires the IFN-␥-inducible guanylate binding proteins (14).…”

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confidence: 99%

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Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages

et al. 2013

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Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that preferentially infects epithelial cells. Professional phagocytes provide C. trachomatis only a limited ability to survive and are proficient killers of chlamydiae. We present evidence herein that identifies a novel host defense protein, perforin-2, that plays a significant role in the eradication of C. trachomatis during the infection of macrophages. Knockdown of perforin-2 in macrophages did not alter the invasion of host cells but did result in chlamydial growth that closely mirrored that detected in HeLa cells. C trachomatis L2, serovar B, and serovar D and C. muridarum were all equally susceptible to perforin-2-mediated killing. Interestingly, induction of perforin-2 expression in epithelial cells is blocked during productive chlamydial growth, thereby protecting chlamydiae from bactericidal attack. Ectopic expression of perforin-2 in HeLa cells, however, does result in killing. Overall, our data implicate a new innate resistance protein in the control of chlamydial infection and may help explain why the macrophage environment is hostile to chlamydial growth.

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Section: Resultssupporting

confidence: 81%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages

et al. 2013

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“…However, unlike epithelial cells, M are not a hospitable niche for chlamydial intracellular replication, as illustrated by the fact that compared to the case in epithelial cells, only a small fraction of chlamydial RBs are detected in M (49). C. trachomatis destruction inside M has been associated with host cell autophagy, a process by which cells degrade cytoplasmic proteins and organelles (49)(50)(51). Also, studies have demonstrated that M autophagy can enhance antigen presentation to T cells (52).…”

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confidence: 99%

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

Vasilevsky¹,

Greub

Nardelli-Haefliger

et al. 2014

Clin Microbiol Rev

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SUMMARY Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide, and despite significant advances in chlamydial research, a prophylactic vaccine has yet to be developed. This Gram-negative obligate intracellular bacterium, which often causes asymptomatic infection, may cause pelvic inflammatory disease (PID), ectopic pregnancies, scarring of the fallopian tubes, miscarriage, and infertility when left untreated. In the genital tract, Chlamydia trachomatis infects primarily epithelial cells and requires Th1 immunity for optimal clearance. This review first focuses on the immune cells important in a chlamydial infection. Second, we summarize the research and challenges associated with developing a chlamydial vaccine that elicits a protective Th1-mediated immune response without inducing adverse immunopathologies.

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Mediation of Interleukin‐23 and Tumor Necrosis Factor–Driven Reactive Arthritis by Chlamydia‐Infected Macrophages in SKG Mice

Romand

Liu

Rahman

et al. 2021

Arthritis & Rheumatology

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Objective ZAP‐70W163C BALB/c (SKG) mice develop reactive arthritis (ReA) following infection with Chlamydia muridarum. Since intracellular pathogens enhance their replicative fitness in stressed host cells, we examined how myeloid cells infected with C muridarum drive arthritis. Methods SKG, Il17a‐deficient SKG, and BALB/c female mice were infected with C muridarum or C muridarum luciferase in the genitals. C muridarum dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti–tumor necrosis factor (anti‐TNF) and anti–interleukin‐23p19 (anti–IL‐23p19) were administered after infection or arthritis onset. Gene expression of Hspa5, Tgtp1, Il23a, Il17a, Il12b, and Tnf was compared in SKG mice and BALB/c mice. Results One week following infection with C muridarum, macrophages and neutrophils were observed to have infiltrated the uteri of mice and were also shown to have carried C muridarum DNA to the spleen. C muridarum load was higher in SKG mice than in BALB/c mice. Macrophage depletion was shown to reduce C muridarum load and prevent development of arthritis. Compared with BALB/c mice, expression of Il23a and Il17a was increased in the uterine and splenic neutrophils of SKG mice. The presence of anti–IL‐23p19 during infection or Il17a deficiency suppressed arthritis. Tnf was overexpressed in the joints of SKG mice within 1 week postinfection, and persisted beyond the first week. TNF inhibition during infection or at arthritis onset suppressed the development of arthritis. Levels of endoplasmic reticulum stress were constitutively increased in the joints of SKG mice but were induced, in conjunction with immunity‐related GTPase, by C muridarum infection in the uterus. Conclusion C muridarum load is higher in SKG mice than in BALB/c mice. Whereas proinflammatory IL‐23 produced by neutrophils contributes to the initiation of C muridarum–mediated ReA, macrophage depletion reduces C muridarum dissemination to other tissues, tissue burden, and the development of arthritis. TNF inhibition was also shown to suppress arthritis development. Our data suggest that enhanced bacterial dissemination in macrophages of SKG mice drives the TNF production needed for persistent arthritis.

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Chlamydia trachomatis vacuole maturation in infected macrophages

Abstract: Macrophages can suppress Chlamydia replication by targeting the bacteria to degradative organelles such as lysosomes.

Cited by 40 publications

References 50 publications

Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages

Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

Mediation of Interleukin‐23 and Tumor Necrosis Factor–Driven Reactive Arthritis by Chlamydia‐Infected Macrophages in SKG Mice

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