Characterization of <i>In Vitro Chlamydia muridarum</i> Persistence and Utilization in an <i>In Vivo</i> Mouse Model of <scp>C</scp>hlamydia Vaccine

Carey, Alison J.; Huston, Wilhelmina M.; Cunningham, Kyle W.; Hafner, Louise M.; Beagley, Kenneth W.

doi:10.1111/aji.12093

Cited by 9 publications

(8 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chlamydia muridarum has been extensively used to study the mechanisms of C. trachomatis pathogenesis and immunity in a mouse model [2]. Intravaginal inoculation of mice with C. muridarum can lead to infection in the lower and upper genital tract, which closely mimics the pathology induced by C. trachomatis in humans [3]. Both animal and human studies have established a vital role for T cell-mediated immunity, predominantly that of IFN- γ -producing CD4 + T cells, and the complementary role of humoral immunity in host resistance to chlamydial infection [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Koroleva

Kobets

Щербинин

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine.

show abstract

Section: Introductionmentioning

confidence: 99%

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Koroleva

Kobets

Щербинин

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry showed Salmonella to be mainly localized extracellularly in the ovarian medulla and within the tubuli seminiferi and between sertoli cells in the male testes. These sites may favor Salmonella persistence through their relative inaccessibility for the host’s immune system [29,30]. Despite Salmonella being considered a chiefly intracellular pathogen, residing in the host macrophages [1,14], extracellular persistence in niches poorly accessible to the immune system provides evidence for multiple pathogen strategies [31].…”

Section: Discussionmentioning

confidence: 99%

Host-pathogen co-existence incurs reproductive costs

Strubbe

Haesendonck

Verbrugghe

et al. 2020

Preprint

View full text Add to dashboard Cite

Widespread endemism of host-adapted pathogens poses a heavy burden on animal and human health. Mechanisms underpinning long-term host pathogen co-existence and concurrent costs are poorly understood. We use infections in pigeons with pathogenic, pigeon adapted Salmonella Typhimurium to explain how host and pathogen trade-offs and benefits sustain long-term pathogen endemism. An experimentally infected group of pigeons that was studied for 15 months showed that pathogen persistence decreased host condition and reproductive success, but conferred protection against Salmonella-induced clinical disease. The relevance of these findings was confirmed in nature, where this pathogen was shown to widely occur in feral pigeons (Columba livia), yet without clinical disease. Pathogen transmission and long-term persistence were associated with intermittent faecal shedding, which markedly increased during crop feeding and natural stress periods. Exploiting host specific traits in the presence of protective host population immunity thus facilitates long-term co-existence, be it at a significant reproductive cost.

show abstract

“…DNA was extracted from isolated M1/M2 macrophages using a QIAamp DNA Mini Kit (Qiagen) according to manufacturers’ instructions. Quantitative 16S ribosomal RNA PCRs were performed on DNA from M1/M2 macrophages according to previously published techniques …”

Section: Methodsmentioning

confidence: 99%

“…Quantitative 16S ribosomal RNA PCRs were performed on DNA from M1/M2 macrophages according to previously published techniques. 45…”

Section: Quantitative Pcrmentioning

confidence: 99%

Chlamydia‐infected macrophages are resistant to azithromycin treatment and are associated with chronic oviduct inflammation and hydrosalpinx development

et al. 2019

Self Cite

View full text Add to dashboard Cite

Chlamydia infection remains the leading sexually‐transmitted bacterial infection worldwide, causing damaging sequelae such as tubal scarring, infertility and ectopic pregnancy. As infection is often asymptomatic, prevention via vaccination is the optimal strategy for disease control. Vaccination strategies aimed at preventing bacterial infection have shown some promise, although these strategies often fail to prevent damaging inflammatory pathology when Chlamydia is encountered. Using a murine model of Chlamydia muridarum genital infection, we employed two established independent models to compare immune responses underpinning pathologic development of genital Chlamydia infection. Model one uses antibiotic treatment during infection, with only early treatment preventing pathology. Model two uses a plasmid‐cured variant strain of C. muridarum that does not cause pathologic outcomes like the plasmid‐containing wild‐type counterpart. Using these infection models, contrasted by the development of pathology, we identified an unexpected role for macrophages. We observed that mice showing signs of pathology had greater numbers of activated macrophages present in the oviducts. This may have been due to early differences in macrophage activation and proinflammatory signaling leading to persistent or enhanced infection. These results provide valuable insight into the cellular mechanisms driving pathology in Chlamydia infection and contribute to the design and development of more effective vaccine strategies for protection against the deleterious sequelae of Chlamydia infection of the female reproductive tract.

show abstract

Characterization of In Vitro Chlamydia muridarum Persistence and Utilization in an In Vivo Mouse Model of Chlamydia Vaccine

Cited by 9 publications

References 49 publications

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Host-pathogen co-existence incurs reproductive costs

Chlamydia‐infected macrophages are resistant to azithromycin treatment and are associated with chronic oviduct inflammation and hydrosalpinx development

Contact Info

Product

Resources

About