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Purpose: This study investigated the effect of 5 days of heat acclimation training on neuromuscular function, intestinal damage, and 20 km cycling (20TT) performance in the heat. Methods: Eight recreationally trained males completed two 5-day training blocks (cycling 60 min day−1 at 50% peak power output) in a counter-balanced, cross-over design, with a 20TT completed before and after each block. Training was conducted in hot (HA: 34.9 ± 0.7 °C, 53 ± 4% relative humidity) or temperate (CON: 22.2 ± 2.6 °C, 65 ± 8% relative humidity) environment. All 20TTs were completed in the heat (35.1 ± 0.5 °C, 51 ± 4% relative humidity). Neuromuscular assessment of knee extensors (5 × 5 s maximum voluntary contraction; MVC) was completed before and after each 20TT and on the first and last days of each training block. Results: MVC torque was statistically higher after 5 days of HA training compared to CON (mean difference = 14 N m [95% confidence interval; 6, 23]; p < 0.001; d = 0.77). However, 20TT performance after 5 days of HA training was not statistically different to CON, with a between-conditions mean difference in the completion time of 68 s [95% confidence interval; − 9, 145] (p = 0.076; d = 0.35). Conclusion: Short-term heat acclimation training may increase knee extensor strength without changes in central fatigue or intestinal damage. Nevertheless, it is insufficient to improve 20 km self-paced cycling performance in the heat compared to workload-matched training in a temperate environment. These data suggest that recreationally trained athletes gain no worthwhile performance advantage from short-term heat-training before competing in the heat.

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. In this study, using mouse testicular cell lines, we examined the impact of infection on testicular cell lineage transcriptomes and potential mechanisms for this impact. The somatic cell lineages exhibited significantly fragmented genomes during infection. Likely resulting from this, each of the Leydig, Sertoli and germ cell lineages experienced extensive transcriptional dysregulation, leading to significant changes in cellular biological pathways, including interferon and germ-Sertoli cell signalling. The cell lineages, as well as isolated spermatozoa from infected mice, also contained globally hypomethylated DNA. Cumulatively, the DNA damage and epigenetic-mediated transcriptional dysregulation observed within testicular cells during chlamydial infection could result in the production of spermatozoa with abnormal epigenomes, resulting in previously observed subfertility in infected animals and congenital defects in their offspring.

Chlamydia pneumoniae can infect the brain and has been linked to late-onset dementia. Chlamydia muridarum, which infects mice, is often used to model human chlamydial infections. While it has been suggested to be also important for modelling brain infection, nervous system infection by C. muridarum has not been reported in the literature. C. pneumoniae has been shown to infect the olfactory bulb in mice after intranasal inoculation, and has therefore been suggested to invade the brain via the olfactory nerve; however, nerve infection has not been shown to date. Another path by which certain bacteria can reach the brain is via the trigeminal nerve, but it remains unknown whether Chlamydia species can infect this nerve. Other bacteria that can invade the brain via the olfactory and/or trigeminal nerve can do so rapidly, however, whether Chlamydia spp. can reach the brain earlier than one-week post inoculation remains unknown. In the current study, we showed that C. muridarum can within 48 h invade the brain via the olfactory nerve, in addition to infecting the trigeminal nerve. We also cultured the glial cells of the olfactory and trigeminal nerves and showed that C. muridarum readily infected the cells, constituting a possible cellular mechanism explaining how the bacteria can invade the nerves without being eliminated by glial immune functions. Further, we demonstrated that olfactory and trigeminal glia differed in their responses to C. muridarum, with olfactory glia showing less infection and stronger immune response than trigeminal glia.

More than 100 million new sexually transmitted infections (STIs) are acquired every day, with 357 million new infections each year caused by chlamydia, gonorrhea, syphilis, and trichomoniasis. At least 500 million people are estimated to have a genital herpes infection. Bacterial STIs are currently treatable with antibiotics, although antibiotic-resistant gonorrhea is becoming a major problem. Antivirals can be used to reduce symptoms and shedding of genital herpes but cannot cure latent infections. To date, vaccines have been developed only against human papillomavirus and hepatitis B, despite the recognition that vaccines represent the best means of halting this hidden STI epidemic. To facilitate successful reproduction, immunity in both the female and male reproductive tracts must be regulated. In females reproductive tract, immunity is regulated by sex hormones during pregnancy to allow successful implantation and growth to term of a semiallogeneic fetus. In males, sperm development begins at puberty, well after tolerance to self has developed. Therefore immune responses in the testes and epididymides must be suppressed to prevent autoimmunity against developing sperm and male infertility. These restraints on reproductive tract immune responses not only may provide opportunities for many sexually transmitted pathogens to establish chronic infections but also represent major challenges to the development of successful vaccines to target the major STIs. In this chapter, we describe how immunity in the female and male reproductive tracts is regulated to facilitate reproduction and discuss current research progress toward the development of vaccines for chlamydia and genital herpes.

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. In animal models, testicular Chlamydia, and potentially other bacterial and viral infections, cause histopathology that is likely to adversely affect spermatogenesis and fertility. This likely occurs through infiltration of inflammatory cells, functional dysregulation of immunosuppressive testicular macrophages and Sertoli cells and destruction of key testicular cell types including sperm progenitors. Here, testicular damage due to infection and/or inflammation is reviewed, as it represents a probable underestimated and unrecognized factor leading to male infertility.

The infectious disease melioidosis is caused by the bacterium Burkholderia pseudomallei. Melioidosis is characterised by high mortality and morbidity and can involve the central nervous system (CNS). We have previously discovered that B. pseudomallei can infect the CNS via the olfactory and trigeminal nerves in mice. We have shown that the nerve path is dependent on mouse strain, with outbred mice showing resistance to olfactory nerve infection. Damage to the nasal epithelium by environmental factors is common, and we hypothesised that injury to the olfactory epithelium may increase the vulnerability of the olfactory nerve to microbial insult. We therefore investigated this, using outbred mice that were intranasally inoculated with B. pseudomallei, with or without methimazole-induced injury to the olfactory neuroepithelium. Methimazole-mediated injury resulted in increased B. pseudomallei invasion of the olfactory epithelium, and only in pre-injured animals were bacteria found in the olfactory nerve and bulb. In vitro assays demonstrated that B. pseudomallei readily infected glial cells isolated from the olfactory and trigeminal nerves (olfactory ensheathing cells and trigeminal Schwann cells, respectively). Bacteria were degraded by some cells but persisted in other cells, which led to the formation of multinucleated giant cells (MNGCs), with olfactory ensheathing cells less likely to form MNGCs than Schwann cells. Double Cap mutant bacteria, lacking the protein BimA, did not form MNGCs. These data suggest that injuries to the olfactory epithelium expose the primary olfactory nervous system to bacterial invasion, which can then result in CNS infection with potential pathogenic consequences for the glial cells.

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. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality.