Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice and is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed CD4 ϩ T cell-mediated protective immunity and a CD8 ϩ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8 ϩ T cells were evaluated, we found, surprisingly, that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice and suggesting a pathogenic mechanism that is independent of CD8 ϩ T cells. We further found that depletion of CD4 ϩ T cells from CD8 ϩ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4 ϩ T cells became pathogenic in mice genetically deficient in CD8 ϩ T cells. Since depletion of CD4 ϩ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8 ϩ T cell-deficient mice, we propose that in the absence of CD8 ϩ T cells, some CD4 ϩ T cells may remain protective (as in C57BL/6J mice), while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms, depending upon host genetics and infection conditions. The CD8 ϩ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4 ϩ T cells promote chlamydial pathogenicity.

Diabetes mellitus (DM) is one of the most fast evolving global issues characterized by hyperglycemia. Patients with diabetes are considered to face with higher risks of adverse cardiovascular events. Those are the main cause of mortality and disability in diabetes patients. There are novel antidiabetic agents that selectively suppress sodium-glucose cotransporter-2 (SGLT-2). They work by reducing proximal tubule glucose reabsorption. Although increasing evidence has shown that SGLT-2 inhibitors can contribute to a series of cardiovascular benefits in diabetic patients, including a reduced incidence of major adverse cardiovascular events and protection of extracardiac organs, the potential mechanisms of SGLT2 inhibitors’ cardiovascular protective effects are still not fully elucidated. Given the important role of inflammation and metabolism in diabetic cardiovascular diseases, this review is intended to rationally compile the multifactorial mechanisms of SGLT-2 inhibitors from the point of immunity, inflammation and metabolism, depicting the fundamental cellular and molecular processing of SGLT-2 inhibitors exerting regulating immunity, inflammation and metabolism. Finally, future directions and perspectives to prevent or delay cardiovascular complications in DM by SGLT-2 inhibitors are presented.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease with insulin deficiency due to pancreatic β cell destruction. Multiple independent cohort studies revealed specific lipid spectrum alterations prior to islet autoimmunity in T1DM. Except for serving as building blocks for membrane biogenesis, accumulative evidence suggests lipids and their derivatives can also modulate different biological processes in the progression of T1DM, such as inflammation responses, immune attacks, and β cell vulnerability. However, the types of lipids are huge and majority of them have been largely unexplored in T1DM. In this review, based on the lipid classification system, we summarize the clinical evidence on dyslipidemia related to T1DM and elucidate the potential mechanisms by which they participate in regulating inflammation responses, modulating lymphocyte function and influencing β cell susceptibility to apoptosis and dysfunction. This review systematically recapitulates the role and mechanisms of various lipids in T1DM, providing new therapeutic approaches for T1DM from a nutritional perspective.

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 gastrointestinal tract co-related 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 swabs. FTY720 treatment significantly delayed live organism shedding in the rectal swabs. However, FTY720 failed to block chlamydial spreading to gastrointestinal tract. The live chlamydial organisms recovered from rectal swabs reached similar levels between mice with or without FTY720 treatment by day 42 in C57BL/6J and day 28 in CBA/J respectively. Thus, genital Chlamydia is able to launch a 2nd wave of spreading via an FTY720-resistant pathway after the 1st wave of spreading was inhibited by FTY720. As a result, all mice developed significant hydrosalpinx. The FTY720-resistant spreading led to stable colonization of chlamydial organisms in the colon. Consistently, FTY720 did not alter the colonization of intracolonically inoculated Chlamydia. Thus, we have demonstrated that, following a delay in chlamydial spreading caused by FTY720, genital Chlamydia is able to both spread to gastrointestinal tract via an FTY720-resistant pathway and to maintain its pathogenicity in the upper genital tract. Further characterization of the FTY720-resistant pathway(s) explored by Chlamydia for spreading to gastrointestinal tract may promote our understanding of Chlamydia pathogenic mechanisms.