Th17‐mediated mucosal inflammation is related to increased Prevotella bacterial abundance. The actual involvement of Prevotella in the development and accumulation of intestinal Th17 cells at a steady state, however, remains undefined. Herein, we investigated the role of Prevotella in inducing intestinal Th17 cells in mice. Mice were treated with a combination of broad‐spectrum antibiotics (including ampicillin, neomycin sulfate, vancomycin hydrochloride, and metronidazole) in their drinking water for 4 weeks and then gavaged with Prevotella for 4 weeks. After inoculation, 16S rDNA sequencing was used to verify the colonization of Prevotella in the colon of mice. The IL‐17A as well as IL‐17A‐expressing T cells was localized and quantified by an immunofluorescence assay (IFA) of colon sections. Th17 cells in the mesenteric lymph nodes of mice were counted by flow cytometry. Systemic immune response to Prevotella colonization was evaluated based on the serum levels of IL‐6, TNF‐ α , IL‐1 β , IL‐17A, IL‐10, IL‐4, IFN‐ γ , and IL‐2. Th17‐polarizing cytokines (IL‐6, TNF‐ α , IL‐1 β , and IL‐2) induced by Prevotella were evaluated by stimulation of bone marrow‐derived dendritic cells (BMDCs). Results revealed that after inoculation, Prevotella successfully colonized the intestine of mice and induced the production and accumulation of colonic Th17 cells in the colon. Moreover, Prevotella elevated some of the Th17‐related cytokines in the serum of mice. And Th17‐polarizing cytokines (IL‐6 and IL‐1 β ) produced by BMDCs were mediated mainly through the interaction between Prevotella and Toll‐like receptor 2 (TLR2). In conclusion, our data suggest that Prevotella induces the production of Th17 cells in the colon of mice, thus highlighting the potential role of Prevotella in training the intestinal immune system.

The programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) signaling pathway is a negative regulatory mechanism that inhibits T cell proliferation and cytokine production. Soluble PD‑1 (sPD‑1) and soluble PD‑L1 (sPD‑L1), are also involved in regulation of the PD‑1/PD‑L1 signaling pathway. In the present study, the expression levels of sPD‑1 and sPD‑L1, as well as those of T helper (Th)1 [including interleukin (IL)‑2 and interferon gamma], Th2 (including IL‑4, IL‑6 and IL‑10) and Th17 (including interleukin 17) cell cytokines, were measured in the sera of patients with cystic echinococcosis (CE). Measurements were performed prior to and following after surgery and treatment with cyclic albendazole to investigate the effects of sPD‑1 and sPD‑L1 in patients with CE. Cytokine expression levels were measured using cytokine bead array and the expression levels of sPD‑1 and sPD‑L1 were measured using ELISA. In addition, in vitro stimulation was used to detect whether sPD‑L1 has a negative regulatory effect on cytokine secretion or homeostasis. The present study observed significantly higher levels of sPD‑L1 in patients with CE compared with healthy controls. Significantly elevated levels of Th2 cytokines in the sera of patients with CE were also observed. The results also suggest that there is an imbalanced expression of Th1 and Th2 cells during CE. In addition, it was demonstrated that sPD‑1 and sPD‑L1 are regulatory factors to the PD‑1/PD‑L1 signaling pathway, each having opposite effect, suggesting that they regulate the immune response to CE infection by creating a dynamic balance. In conclusion, sPD-L1 may play an important role in maintaining homeostasis in hosts with CE.

Invasive fungal infections especially in immunocompromised patients represent a dominating cause of mortality. The most commonly used antifungal agents can be divided into three broad categories, including triazoles, echinocandins and polyenes. Antifungal resistance is on the increase, posing a growing threat to the stewardship of immunocompromised patients with fungal infections. The paucity of currently available antifungals leads to the rapid emergence of drug resistance and thus aggravates the refractoriness of invasive fungal infections. Therefore, deep exploration into mechanisms of drug resistance and search for new antifungal targets are required. This review highlights the therapeutic strategies targeting Hsp90, calcineurin, trehalose biosynthesis and sphingolipids biosynthesis, in an attempt to provide clinical evidence for overcoming drug resistance and to form the rationale for combination therapy of conventional antifungals and agents with novel mechanisms of action. What’s more, this review also gives a concise introduction of three new-fashioned antifungals, including carboxymethyl chitosan, silver nanoparticles and chromogranin A-N46.

There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.

Tuberculosis (TB), predominantly caused by Mycobacterium tuberculosis (MTB) infection, remains a prominent global health challenge. Macrophages are the frontline defense against MTB, relying on autophagy for intracellular bacterial clearance. However, MTB can combat and evade autophagy, and it influences macrophage polarization, facilitating immune evasion and promoting infection. We previously found that heparin-binding hemagglutinin (HBHA) inhibits autophagy in A549 cells; however, its role in macrophage autophagy and polarization remains unclear. Bacterial cultures, cell cultures, western blotting, immunofluorescence, macrophage infection assays, siRNA knockdown, and ELISA were used to investigate HBHA’s impact on macrophages and its relevance in Mycobacterium infection. HBHA inhibited macrophage autophagy. Expression of recombinant HBHA in Mycobacterium smegmatis (rMS-HBHA) inhibited autophagy, promoting bacterial survival within macrophages. Conversely, HBHA knockout in the Mycobacterium bovis Bacillus Calmette-Guérin (BCG) mutant (BCG-ΔHBHA) activated autophagy and reduced bacterial survival. Mechanistic investigations revealed that HBHA may inhibit macrophage autophagy through the TLR4-dependent PI3K-AKT-mTOR signaling pathway. Furthermore, HBHA induced macrophage M2 polarization. Mycobacterium may exploit HBHA to suppress the antimicrobial immune response in macrophages, facilitating intracellular survival, and immune evasion through autophagy inhibition and M2 polarization induction. Our findings may help identify novel therapeutic targets and develop more effective treatments against MTB infection.

Airway epithelial cell is often the initial site of attack by pathogens, and cell death is commonly caused by internalization of Mycobacterium tuberculosis (Mtb). However, the mechanism of interaction between epithelial cells and Mtb is not well understood. In this study, we investigated the role of the heparin-binding hemagglutinin (HBHA) protein of Mtb in the function of epithelial cells. In particular, the autophagy of A549 cells was determined based on microtubule-associated protein 1 light chain 3 alpha (LC3) activity. Autophagosome formation was detected by Monodansylcadaverine (MDC) staining and immune fluorescence staining of LC3. Autophagy could be significantly suppressed by HBHA protein. In addition, the LDH assay results showed that HBHA treatment could induce death on A549 cells. To explore the form of cell death, we detected the activity of caspase-3 and LDH release of A549 cells in the presence or absence of caspase inhibitor Z-VAD-FMK. Results demonstrated that HBHA treatment could induce apoptosis of A549 cells. To further confirm these results, we constructed the recombinant Mycobacterium smegmatis (MS) expressing HBHA (rMS-HBHA) and explored the influence of rMS-HBHA on the function of A549 cells. rMS-HBHA infection significantly inhibited LC3 expression and the maturation of autophagosomes in A549 cells. Subsequently, we infected A549 cells with MS and detected the viability of intracellular MS by CFU counts. rMS-HBHA showed higher survival and replication capacity in A549 cells than those of the wild-type MS. Finally, infection of A549 cells with rMS-HBHA caused further apoptosis. These findings suggested that rMS-HBHA could inhibit autophagy, promote its survival and replication within A549 cells, and subsequently induce apoptosis on infected cells to facilitate infection.