Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection.

Chlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract.

IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8 T cell responses.

Chlamydia trachomatis infections are an important sexually transmitted infection that can lead to inflammation, scarring and hydrosalpinx/infertility. However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown.

Enhanced clearance of C. muridarum infection using azithromycin-loaded liposomes.

Chlamydia trachomatis is an intracellular bacterium which infects around 129 million people annually. Despite similar infection rates between sexes, most research investigating the effects of chlamydial infection on fertility has focused on females. There is now emerging evidence of a potential link between Chlamydia and impaired male fertility.

Retroviral b-Zip protein (HBZ) contributes to the release of soluble and exosomal immune checkpoint molecules in the context of neuroinflammation.

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive, neuroinflammatory demyelinating condition of the spinal cord. We have previously shown that aberrant expression and activity of immune checkpoint (ICP) molecules such as PD-1 and PD-L1/PD-L2, negatively associates with the cytolytic potential of T cells in individuals with HAM/TSP. Interestingly, ICPs can exist in a soluble cell-free form and can be carried on extracellular vesicles (EVs) and exosomes (small EVs, <300nm) while maintaining their immunomodulatory activity.

Pathogenic NKT cells attenuate urogenital chlamydial clearance and enhance infertility.

Urogenital chlamydial infections continue to increase with over 127 million people affected annually, causing significant economic and public health pressures. While the role of traditional MHCI and II peptide presentation is well defined in chlamydial infections, the role of lipid antigens in immunity remains unclear. Natural killer (NK) T cells are important effector cells that recognize and respond to lipid antigens during infections.

Prophylactic and therapeutic vaccination protects sperm health from Chlamydia muridarum-induced abnormalities.

Chlamydia is the most common bacterial sexually transmitted infection worldwide and it is widely acknowledged that controlling the rampant community transmission of this infection requires vaccine development. In this study, for the first time, we elucidate the long-term response to male mouse chlamydial vaccination with chlamydial major outer membrane protein (MOMP) and ISCOMATRIX (IMX) both prophylactically and in a novel therapeutic setting. Vaccination significantly reduced and, in some cases, cleared chlamydial burden from the prostates, epididymides, and testes, which correlates with high IgG and IgA tires in tissues and serum.

Reduction of unnecessary antibiotic days in a level IV neonatal intensive care unit.

Objective: Antibiotics are widely prescribed in the neonatal intensive care unit (NICU) and duration of prescription is varied. We sought to decrease unnecessary antibiotic days for the most common indications in our outborn level IV NICU by 20% within 1 year.

Design And Interventions: A retrospective chart review was completed to determine the most common indications and treatment duration for antibiotic therapy in our 39-bed level IV NICU.

Severity of neonatal influenza infection is driven by type I interferon and oxidative stress.

Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are antiviral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza virus (IV) model, which demonstrates increased mortality.

Evaluation of the applicability of the current CDC pediatric ventilator-associated events (PedVAE) surveillance definition in the neonatal intensive care unit population.

Background: There is limited data on pediatric ventilator-associated events (PedVAE) in the neonatal intensive care unit (NICU) setting, since the CDC mandated state reporting of these events in January 2019. This study sought to describe PedVAE rates and characteristics in the NICU population.

Methods: Single-center case-control study of infants requiring mechanical ventilation in a 39-bed level IV NICU between January 1, 2018 and December 31, 2020.

MicroRNA-139 Expression Is Dispensable for the Generation of Influenza-Specific CD8 T Cell Responses.

MicroRNAs (miRNAs/miRs) are small, endogenous noncoding RNAs that are important post-transcriptional regulators with clear roles in the development of the immune system and immune responses. Using miRNA microarray profiling, we characterized the expression profile of naive and in vivo generated murine effector antiviral CD8 T cells. We observed that out of 362 measurable mature miRNAs, 120 were differentially expressed by at least 2-fold in influenza-specific effector CD8 CTLs compared with naive CD8 T cells.

Eliminating Contamination in Umbilical Cord Blood Culture Sampling for Early-Onset Neonatal Sepsis.

Despite the advantages of umbilical cord blood culture (UCBC) use for diagnosis of early onset sepsis (EOS), contamination rates have deterred neonatologists from its widespread use. We aimed to implement UCBC collection in a level III neonatal intensive care unit (NICU) and apply quality improvement (QI) methods to reduce contamination in the diagnosis of early onset sepsis. Single-center implementation study utilizing quality improvement methodology to achieve 0% contamination rate in UCBC samples using the Plan-Do-Study-Act (PDSA) model for improvement.

Chitin-Derived AVR-48 Prevents Experimental Bronchopulmonary Dysplasia (BPD) and BPD-Associated Pulmonary Hypertension in Newborn Mice.

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay.

A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells.

Innate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILC) that to our knowledge has not been previously identified.

DNA damage contributes to transcriptional and immunological dysregulation of testicular cells during Chlamydia infection.

Chlamydia is the most commonly reported sexually transmitted bacterial infection, with 127 million notifications worldwide each year. Both males and females are susceptible to the pathological impacts on fertility that Chlamydia infections can induce. However, male chlamydial infections, particularly within the upper reproductive tract, including the testis, are not well characterized.

Testicular inflammation and infertility: Could chlamydial infections be contributing?

Despite the global incidence of both male infertility and sexually transmitted infections rising each year, the relationship between the two is relatively unstudied. Chlamydia is the most common bacterial sexually transmitted pathogen; however, the majority of research remains focussed on women, while the role of infection and resulting immunopathology in male factor infertility is largely unknown. Chlamydia was found in testicular biopsies from asymptomatic men with idiopathic infertility, which highlights this potential role.

α1,3-Fucosyltransferase-IX, an enzyme of pulmonary endogenous lung stem cell marker SSEA-1, alleviates experimental bronchopulmonary dysplasia.

Background: Endogenous pulmonary stem cells (PSCs) play an important role in lung development and repair; however, little is known about their role in bronchopulmonary dysplasia (BPD). We hypothesize that an endogenous PSC marker stage-specific embryonic antigen-1 (SSEA-1) and its enzyme, α1,3-fucosyltransferase IX (FUT9) play an important role in decreasing inflammation and restoring lung structure in experimental BPD.

Methods: We studied the expression of SSEA-1, and its enzyme FUT9, in wild-type (WT) C57BL/6 mice, in room air and hyperoxia.

Chronic testicular Chlamydia muridarum infection impairs mouse fertility and offspring development†.

With approximately 131 million new genital tract infections occurring each year, Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown.

Group B Streptococcus serotypes Ia and V induce differential vaginal immune responses that may contribute to long term colonization of the female reproductive tract.

Problem: Group B Streptococcus (GBS) is a common colonizer of the female genital tract at the time of pregnancy and has been associated with severe neonatal infections. Despite trials for GBS vaccines already being underway, the factors influencing vaginal GBS colonization and clearance are currently poorly understood.

Method Of Study: Within this study, we investigated the host immune responses to GBS infections in mice that affect GBS vaginal colonization and clearance.

Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG.

Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection.

Detection of chlamydia infection within human testicular biopsies.

Study Question: Can Chlamydia be found in the testes of infertile men?

Summary Answer: Chlamydia can be found in 16.7% of fresh testicular biopsies and 45.3% of fixed testicular biopsies taken from a selection of infertile men.

Rodent Infections for Chlamydia spp.

Chlamydia spp. infections cause immunopathology of the male and female urogenital tracts and incidence continues to rise across the globe. Animal models offer the opportunity to study the host: pathogen relationship, with rodent models being an attractive first step in studying immune interactions, genetic knockout, as well as bacterial inhibitor and vaccine trials.

Hematogenous dissemination of Chlamydia muridarum from the urethra in macrophages causes testicular infection and sperm DNA damage†.

The incidence of Chlamydia infection, in both females and males, is increasing worldwide. Male infections have been associated clinically with urethritis, epididymitis, and orchitis, believed to be caused by ascending infection, although the impact of infection on male fertility remains controversial. Using a mouse model of male chlamydial infection, we show that all the major testicular cell populations, germ cells, Sertoli cells, Leydig cells, and testicular macrophages can be productively infected.

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

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.

Dissecting the defects in the neonatal CD8 T-cell response.

The neonatal period presents a complex scenario where the threshold of reactivity toward colonizing microbiota, maternal antigens, autoantigens, and pathogens must be carefully moderated and balanced. CD8 T cells are critical for the response against intracellular bacteria and viruses, but this immune compartment maintains altered function relative to adult counterparts because of the unique challenges which infants face. Here, we review our current understanding of the factors which may promote the attenuation and altered function of the neonatal CD8 T-cell response and potential avenues for future study.