The reaction of innate lymphoid cells in the mouse female genital tract to chlamydial infection

2021 ◽  
Author(s):  
Svenja Barth ◽  
Susanne Kirschnek ◽  
Noemi Ortmann ◽  
Yakup Tanriver ◽  
Georg Häcker

Background Innate lymphoid cells (ILCs) are comprised of five distinct subsets. ILCs are found at mucosal barriers and may fight invading pathogens. Chlamydia is an intracellular bacterium that infects the mucosa of the genital tract and can cause severe tissue damage. Methods We used a mouse infection model with Chlamydia muridarum ( Cmu ) to measure the reaction of genital tract ILCs to the infection. Results Tissue resident natural killer cells were the largest group in the uninfected female genital tract, and their number did not substantially change. Conventional NK cells were present at the greatest numbers during acute infection, while ILC1 cells continuously increased to high numbers. ILC2 and ILC3 cells were found at lower numbers that oscillated by a factor of 2-4. The majority of ILC3 transdifferentiated into ILC1 cells. NK cells and ILC1 cells produced IFN-γ and, rarely, TNF, but only early in the infection. Lack of B and T cells increased, while the loss of myeloid cells decreased ILC numbers. ILCs accumulated to high density in the oviduct, a main site of tissue destruction. Conclusions ILC subsets are part of the inflammatory and immune reaction during infection with Cmu and may contribute to tissue damage during chlamydial infection.

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Anne Piantadosi ◽  
Catherine A. Freije ◽  
Christina Gosmann ◽  
Simon Ye ◽  
Daniel Park ◽  
...  

ABSTRACTHeterosexual transmission of human immunodeficiency virus type 1 (HIV-1) is associated with a significant bottleneck in the viral quasispecies population, yet the timing of that bottleneck is poorly understood. We characterized HIV-1 diversity in the blood and female genital tract (FGT) within 2 weeks after detection of infection in three women enrolled in a unique prospective cohort in South Africa. We assembled full-length HIV-1 genomes from matched cervicovaginal lavage (CVL) samples and plasma. Deep sequencing allowed us to identify intrahost single-nucleotide variants (iSNVs) and to characterize within-sample HIV-1 diversity. Our results demonstrated very little HIV-1 diversity in the FGT and plasma by the time viremia was detectable. Within each subject, the consensus HIV-1 sequences were identical in plasma and CVL fluid. No iSNV was present at >6% frequency. One subject had 77 low-frequency iSNVs across both CVL fluid and plasma, another subject had 14 iSNVs in only CVL fluid from the earliest time point, and the third subject had no iSNVs in CVL fluid or plasma. Overall, the small amount of diversity that we detected was greater in the FGT than in plasma and declined over the first 2 weeks after viremia was detectable, compatible with a very early HIV-1 transmission bottleneck. To our knowledge, our study represents the earliest genomic analysis of HIV-1 in the FGT after transmission. Further, the use of metagenomic sequencing allowed us to characterize other organisms in the FGT, including commensal bacteria and sexually transmitted infections, highlighting the utility of the method to sequence both HIV-1 and its metagenomic environment.IMPORTANCEDue to error-prone replication, HIV-1 generates a diverse population of viruses within a chronically infected individual. When HIV-1 is transmitted to a new individual, one or a few viruses establish the new infection, leading to a genetic bottleneck in the virus population. Understanding the timing and nature of this bottleneck may provide insight into HIV-1 vaccine design and other preventative strategies. We examined the HIV-1 population in three women enrolled in a unique prospective cohort in South Africa who were followed closely during the earliest stages of HIV-1 infection. We found very little HIV-1 diversity in the blood and female genital tract during the first 2 weeks after virus was detected in the bloodstream. These results are compatible with a very early HIV-1 population bottleneck, suggesting the need to study the HIV-1 population in the female genital tract before virus is detectable in the bloodstream.


2000 ◽  
Vol 68 (1) ◽  
pp. 192-196 ◽  
Author(s):  
Hua Su ◽  
Ronald Messer ◽  
William Whitmire ◽  
Scott Hughes ◽  
Harlan D. Caldwell

ABSTRACT Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4+ T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log10) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.


The Lancet ◽  
1983 ◽  
Vol 322 (8349) ◽  
pp. 578-579
Author(s):  
G Forster ◽  
R Jha ◽  
D Cheetham ◽  
P Munday ◽  
D Coleman ◽  
...  

2021 ◽  
Author(s):  
Sivasankaran Munusamy Ponnan ◽  
Kannan Thiruvengadam ◽  
Chaitanya Tellapragada ◽  
Anoop T Ambikan ◽  
Aswathy Narayanan ◽  
...  

The female genital tract (FGT) is an essential site of HIV infection. Discerning the nature of HIV-specific local immune responses is crucial for identifying correlates of protection in HIV-exposed seronegative (HESN) individuals. The present study involved a comprehensive analysis of soluble immune mediators, secretory immunoglobulins (sIg) and levels of natural killer (NK) cells, CXCR5 + CD8 + T cells, T follicular helper cells (Tfh) and T regulatory cells (T regs) in the vaginal mucosa, as well as the nature and composition of the cervicovaginal microbiome in HESN women. We found significantly elevated antiviral cytokines, soluble immunoglobulins, and increased frequencies of activated NK cells, CXCR5 + CD8 + T cells and Tfh cells in HESN females as compared to HIV unexposed healthy (UH) women. Analysis of the genital microbiome of HESN women revealed a greater bacterial diversity and increased abundance of Gardnerella spp in the mucosa of HESN women. The findings suggest the female genital tract of HESN females represents a microenvironment equipped with innate immune factors, antiviral mediators and critical T cells subsets that protect against HIV infection.


1985 ◽  
Vol 12 (2) ◽  
pp. 68-71 ◽  
Author(s):  
ERIC M. C. DUNLOP ◽  
BENG T. GOH ◽  
SOHRAB DAROUGAR ◽  
RALPH WOODLAND

Sign in / Sign up

Export Citation Format

Share Document