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Identification of collaborative cross mouse strains susceptible to chlamydial induction of hydrosalpinx.

Sexually transmitted infection with Chlamydia trachomatis can cause pathology, such as hydrosalpinx, in the upper genital tract, leading to infertility. To investigate how genetic variation affects chlamydial pathogenicity, we screened five strains of Collaborative Cross (CC) mice for susceptibility to intravaginal infection and hydrosalpinx induction by C. muridarum, a mouse-adapted chlamydial species used extensively to reveal chlamydial pathogenic mechanisms. In terms of susceptibility to genital chlamydial infection, the five CC strains fell into two categories: CC011 and CC012 were resist

Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): examining the role of niche-specific genes in the evolution of the Chlamydiaceae.

The genome of Chlamydophila caviae (formerly Chlamydia psittaci, GPIC isolate) (1 173 390 nt with a plasmid of 7966 nt) was determined, repr … ed cysteine proteases. One gene cluster (guaBA-add) in the RTR is much more similar to orthologs in Chlamydia muridarum than those in the phylogenetically closest species C.pneumoniae, suggesting the possibility of horizontal transfer of genes between the rodent-associated Chlamydiae. With most genes observed in the other chlamydial genomes represented, C.caviae prov …

CD103+ lung dendritic cells (LDCs) induce stronger Th1/Th17 immunity to a bacterial lung infection than CD11bhi LDCs.

Recent studies suggest differential roles for CD103+ and CD11bhi lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11bhi LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two…

Interleukin-22 promotes T helper 1 (Th1)/Th17 immunity in chlamydial lung infection.

The role of interleukin-22 (IL-22) in intracellular bacterial infections is a controversial issue, although the contribution of this cytokine to host defense against extracellular bacterial pathogens has been well established. In this study, we focused on an intra-cellular bacterium, Chlamydia, and evaluated the production and function of IL-22 in host defense against chlamydial lung infection using a mouse model. We found that Chlamydia muridarum infection elicited quick IL-22 responses in the lung, which increased during infection and were reduced when bacterial loads decreased. More importa…

Invariant and Diverse NKT Cells Regulate Bacterial Clearance and Pathology in Chlamydial Genital Tract Infection in Mice.

Chlamydia trachomatis infection causes pelvic inflammatory disease and infertility, but how host immune factors control pathogen clearance or pathology is not fully understood. Using a mouse model of genital tract infection with Chlamydia muridarum, we examined the role of CD1d-restricted Natural killer T (NKT) cells. Invariant NKT cell-deficient mice (Jα18-/-) showed prolonged vaginal shedding of infectious elementary bodies (EBs), delayed clearance, and decreased early cytokine production compared to wild-type (WT) controls. Conversely, CD1d-/- mice, which lack both invariant and diverse NKT…

Hepatitis B core virus-like particles bearing Pgp3 antigen enhance immune response against genital chlamydial infection in mice.

Chlamydia trachomatis Pgp3 protein-induced immunoprotection is effective but incomplete, which requires the suitable adjuvants to enhance it … e HBc-Pgp3 formulation was instrumental in augmenting IFN-γ production, enhancing the efficiency of Chlamydia muridarum clearance post-challenge, and severity of hydrosalpinx within the lower genital tract. Collectively, these findings illuminate the potential of the novel HBc-Pgp3 chimeric construct as an innovative vaccine candidate, offering augmented immunoprotec …

Protective immunity against mouse upper genital tract pathology correlates with high IFNγ but low IL-17 T cell and anti-secretion protein antibody responses induced by replicating chlamydial organisms in the airway.

To search for optimal immunization conditions for inducing protective immunity against upper genital tract pathologies caused by chlamydial intravaginal infection, we compared protection efficacy in mice immunized intranasally or intramuscularly with live or inactivated Chlamydia muridarum organisms. Mice immunized intranasally with live organisms developed strong protection against both vaginal shedding of infectious organisms and upper genital tract pathologies. The protection correlated with a robust antigen-specific T cell response with high IFNγ but low IL-17. Although a significant level…

Regulation of chlamydial spreading from the small intestine to the large intestine by IL-22-producing CD4+ T cells.

Following an oral inoculation, Chlamydia muridarum descends to the mouse large intestine for long-lasting colonization. However, a mutant C. muridarum that lacks the plasmid-encoded protein pGP3 due to an engineered premature stop codon (designated as CMpGP3S) failed to do so even following an intrajejunal inoculation. This was because a CD4+ T cell-dependent immunity prevented the spread of CMpGP3S from the small intestine to the large intestine. In the current study, we found that mice deficient in IL-22 (IL-22-/-) allowed CMpGP3S to spread from the small intestine to the large intestine on …

CCR2 Enhances Anti-Intracellular Bacterial Infection by Modulating Macrophage Pyroptosis to Rebalance Th Immune Responses.

The treatment of intracellular bacterial infections such as Chlamydia remains a significant clinical challenge due to rising antibiotic resistance and persistent, immunopathology-driven tissue damage. Macrophages are essential for host defense; they can originate from both tissue-resident precursors and circulating monocytes. During infection, macrophages at infected sites are largely derived from monocytes that migrate and differentiate there, where they phagocytose pathogens and orchestrate immune responses. The chemokine receptor CCR2 is a key regulator of this process, yet its role beyond

Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due t … 1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical s …

Chlamydiaceae: Diseases in Primary Hosts and Zoonosis.

Bacteria of the Chlamydiaceae family are a type of Gram-negative microorganism typified by their obligate intracellular lifestyle. The majority of the members in the Chlamydiaceae family are known pathogenic organisms that primarily infect the host mucosal surfaces in both humans and animals. For instance, Chlamydia trachomatis is a well-known etiological agent for ocular and genital sexually transmitted diseases, while C. pneumoniae has been implicated in community-acquired pneumonia in humans. Other chlamydial species such as C. abortus, C. caviae, C. felis, C. muridarum, C. pecorum, and C.

Endogenous IL-17A mediated neutrophil infiltration by promoting chemokines expression during chlamydial lung infection.

Chlamydia is an obligate intracellular bacteria, which can infect cervix, urethra, conjunctiva, joints, lungs and so on. Neutrophils are important in host protection against microbial invasion during the early phase of infection. Here, to investigate the mechanism of IL-17A in recruiting neutrophils during Chlamydia muridarum (Cm) lung infection, we introduced IL-17A antibodies and IL-17-/- mice to confirm the effect of IL-17A on influencing neutrophil attractants expressions. From the analysis of the data, we found that showed that Cm infection could upregulate the expression of neutrophil-re…

Anti-chlamydial Th17 responses are controlled by the inducible costimulator partially through phosphoinositide 3-kinase signaling.

We previously showed that mice deficient in the Inducible Costimulator ligand (ICOSL-KO) develop more severe disease and lung pathology with delayed bacterial clearance upon respiratory infection of Chlamydia muridarum. Importantly, the exacerbation of disease in ICOSL-KO mice was seen despite heightened IFN-γ/Th1 responses, the major defense mechanisms against Chlamydia. To gain insight into the mechanism of ICOS function in this model, we presently analyzed anti-Chlamydia immune responses in mice lacking the entire ICOS (ICOS-KO) versus knock-in mice expressing a mutant ICOS (ICOS-Y181F) tha…

IL-23 receptor signaling licenses group 3-like innate lymphoid cells to restrict a live-attenuated oral Chlamydia vaccine in the gut.

An IFNγ-susceptible mutant of Chlamydia muridarum is attenuated in pathogenicity in the genital tract and was recently licensed as an intracellular Oral vaccine vector or intrOv. Oral delivery of intrOv induces transmucosal protection in the genital tract, but intrOv itself is cleared from the gut (without shedding any infectious particles externally) by IFNγ from group 3-like innate lymphoid cells (ILC3s). We further characterized the intrOv interactions with ILC3s in the current study, since the interactions may impact both the safety and efficacy of intrOv as an oral Chlamydia vaccine. Intr…

A unique insight into the MiRNA profile during genital chlamydial infection.

BACKGROUND: Genital C. trachomatis infection may cause pelvic inflammatory disease (PID) that can lead to tubal factor infertility (TFI). Understanding the pathogenesis of chlamydial complications including the pathophysiological processes within the female host genital tract is important in preventing adverse pathology. MicroRNAs regulate several pathophysiological processes of infectious and non-infectious etiologies. In this study, we tested the hypothesis that the miRNA profile of single and repeat genital chlamydial infections will be different and that these differences will be time depe

Inhibition of the Protein Phosphatase CppA Alters Development of Chlamydia trachomatis.

Chlamydiae are obligate intracellular Gram-negative bacterial pathogens that undergo an essential, but poorly understood, biphasic developme … ificantly reduced CppA activity in vitro and the growth of C. trachomatis L2, C. trachomatis D, and Chlamydia muridarum in a cell culture infection model. The inhibition of C. trachomatis L2 growth was more pronounced when treated at earlier infection time points, and the removal of the inhibitors after 12 h postinfection did not rescue progeny production. Our findin …

Diverse requirements for SRC-family tyrosine kinases distinguish chlamydial species.

UNLABELLED: Chlamydiae are well known for their species specificity and tissue tropism, and yet the individual species and strains show remarkable genomic synteny and share an intracellular developmental cycle unique in the microbial world. Only a relatively few chlamydial genes have been linked to specific disease or tissue tropism. Here we show that chlamydial species associated with human infections, Chlamydia trachomatis and C. pneumoniae, exhibit unique requirements for Src-family kinases throughout their developmental cycle. Utilization of Src-family kinases by C. trachomatis includes ty

Effects of Immunomodulatory Drug Fingolimod (FTY720) on Chlamydia Dissemination and Pathogenesis.

Fingolimod (FTY720), an FDA-approved immunomodulatory drug for treating multiple sclerosis, is an agonist of sphingosine-1-phosphate receptor (S1PR), which has been used as a research tool for inhibiting immune cell trafficking. FTY720 was recently reported to inhibit Chlamydia dissemination. Since genital Chlamydia spreading to the gastrointestinal tract correlated with its pathogenicity in the upper genital tract, we evaluated the effect of FTY720 on chlamydial pathogenicity in the current study. Following an intravaginal inoculation, live chlamydial organisms were detected in mouse rectal s

Совместная доставка амфипольно-конвергента с антигеном и адъютантными комбинациями повышает иммунную защиту, создаваемую вакциной на основе мембранного белка против мукозалов с хламидией.

ВВЕДЕНИЕ: Хламидиальные инфекции распространяются во всем мире, и для борьбы с этим патогеном необходима вакцина. Цель этого исследования состояла в том, чтобы определить, улучшит ли вакцину доставка аппендицита, связанного с антигеном, с помощью деривативизированного амфиполя и адъютантных комбинаций. МЕТОДЫ: Был использован новый подход, заключающийся в том, что хламидийный муридарум (Cm) коренной MOMP (nMOMP) с амфиполями (A8-35) с кавалентно смешанным пептидом (EP67). Включены следующие лица: EP67, либо связанный с A8-35, который использовался для ловушки NMOMP (nMOMP/EP67-A8-35), либо сво

Совпадение в аннотации оригинала
INTRODUCTION: Chlamydial infections are spread worldwide and a vaccine is needed to control this pathogen. The goals of this study were to determine if the delivery of an adjuvant associated to the antigen, via a derivatized amphipol, and adjuvant combinations improve vaccine protection. METHODS: A novel approach, trapping the Chlamydia muridarum (Cm) nativ…

Chlamydial induction of hydrosalpinx in 11 strains of mice reveals multiple host mechanisms for preventing upper genital tract pathology.

The female lower genital tract is constantly exposed to microbial infection, some of which can ascend to and cause pathology such as hydrosalpinx in the upper genital tract, which can affect fertility. To understand host mechanisms for preventing upper genital tract pathology, we screened 11 inbred strains of mice for hydrosalpinx induction by C. muridarum. When examined on days 60 to 80 after intravaginal infection, the 11 strains fell into 3 groups based on their hydrosalpinx severity: CBA/J and SJL/J mice were highly susceptible with a hydrosalpinx score of 5 or greater; Balb/c, C57BL/6J, C