Treatment of postoperative infectious complications in patients with human immunodef iciency virus infection

BACKGROUND: Antibiotics are widely given for surgical patients to prevent infection. Because of the lack of study on the rational use of antibiotics in patients with human immunodef iciency virus(HIV)-infected during surgical procedures, we analyzed the risk factors affecting postoperative infectious complications in HIV-infected patients and explore the rational use of perioperative antibiotics.METHODS: This retrospective study consisted of 308 HIV-infected patients, 272 males and 36 females, who had undergone operation at the Shanghai Public Health Clinical Center from November 2008 to April 2012. The patients were divided into postoperative infection and non-infection groups. Their age and clinical variables were compared. The correlation between surgical incision, surgical site infection(SSI) and postoperative sepsis was analyzed. Prophylactic antibiotics were used for patients with type I and II incisions for less than 2 days. Patients with type III incisions were given antibiotics until the infection was controlled. Antiretroviral therapy(ART) was prescribed preoperatively for patients whose preoperative CD4 count was <350 cells/μL. For those patients whose preoperative CD4 count was <200 cells/μL, sulfamethoxazole and fluconazole were given preoperatively as prophylactic agents controlling Pneumocystis carinii pneumonia and fungal infection.RESULTS: A total of 196 patients developed postoperative infectious complications, and 7 patients died. Preoperative CD4 counts, ratio of CD4/CD8 cells, hemoglobin level, and postoperative CD4 counts, hemoglobin and albumin levels were risk factors of perioperative infection in HIV-infected patients. Patients with a preoperative CD4 count <200 cell/μL, anemia, a postoperative CD4 count <200 cell/μL or albumin levels <35 g/L were correlated with a higher rate of perioperative infection. There was a signif icant correlation between SSI and the type of surgical incision. The rate of SSI in patients with type I surgical incision was 2% and in those with type II surgical incision was 38%. All the patients who received type III surgical incision developed SSI, and they were more likely to develop postoperative sepsis.CONCLUSIONS: HIV-infected patients are more likely to develop postoperative infectious complications. The rational use of antibiotics in HIV-infected patients could help to reduce the rate of postoperative infectious complications in these patients.

Romance of the three kingdoms: RORgammat allies with HIF1alpha against FoxP3 in regulating T cell metabolism and differentiation

Regulatory T(Treg)cells play an essential role in immune homeostasis by controlling the function of various immune effector cells,including RAR-related orphan receptor gammat+(RORγt+)T helper 17(Th17)cells.Foekhead box P3(FoxP3)is the master regulator of Treg cell function,while RORγt is the key transcription factor for the induction of the interleukin(IL)-17 family of cytokines during Th17 cell differentiation.FoxP3 can directly interact with and negatively regulate the function of RORγt,to determine the balance between induced Treg(iTreg)and Th17 cell polarization.Two recent independent studies from the Pan and Chi Labs have shown how hypoxia-inducible factor 1 alpha(HIF1α)is able to tip the balance of T cell differentiation toward the Th17 lineage by responding to the local changes in metabolic shift or an increase in proinflammatory mediators in the microenvironment.By allying with HIF1α,RORγt wins the fight against FoxP3 and Treg cell commitment.

Identification and functional analysis of heterogeneous FOXP3^+ Treg cell subpopulations in human pancreatic ductal adenocarcinoma

CD4^＋ CD25^＋ regulatory T （Treg） cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes （TDLNs） has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor- and TDLN-infiltrating Treg cells remains unclear. Here we provide heterogeneity analysis of tumor infiltrating human CD4^＋ Treg cells and their matched adjacent tissues and TDLNs. We defined three different subpopulations of tumor- and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma （PDAC） and confirmed their functional heterogeneity. Helios^＋ CCR8^＋ Treg cells with potent suppressor function and limited IL-2 and IFN-7 secretion were identified in tumors and TDLNs. On the contrary, Helios^- CCR8^- Treg cells have impaired suppressive activity, and elevated expression of pro-inflammatory cytokines. More advanced grades of PDAC have predominantly Helios^＋ CCR8^＋ Treg cells and few Helios^- CCR8^- Treg cells both in tumors and TDLNs that suggests poor prognosis. These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.

Understanding and therapeutically modulating the stability of regulatory T cells to treat inflammatory diseases

Forkhead box P3(FOXP3)^+regulatory T(Treg)cells are crucial for the homeostasis of the immune system,and harbor suppressive capacities of which are maintained by or inherited with distinct epigenetic signatures.The functional features of Treg cells are facilitated by multiple T cell differentiation-related transcription factors that therefore endow them with adaption capability to dynamic microenvironments.Recent studies also recalled the importance of immune cell metabolism,which is intimately linked with Treg cell differentiation,proliferation and function.Understanding the molecular mechanism underlying the functional stability of Treg cells could provide therapeutic opportunities to treat major human inflammatory diseases including infection,autoimmunity,allergy and cancer.

FOXP3 ＋ regulatory T cells and their functional regulation

FOXP3＋ regulatory T （Treg） cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease （GVHD） and cancer.

Th17 Cells in autoimmune diseases

Th17 cells are a new subset of CD4^＋ T cells fungi. Accumulating evidence suggests that Tb17 cells involved in the clearance of extracellular pathogens and and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren＇s syndrome, inflammatory bowel disease, and multiple sclerosis.

Tissue resident regulatory T cells： novel therapeutic targets for human disease

Over the past decade, the ability of regulatory T cells （Tregs） to suppress multiple types of immune cells has received tremendous attention. Mounting evidence has revealed that tissue resident Tregs control non-immunological processes of their target tissues and contribute to a plethora of human diseases. The identification of novel tissue-specific Tregs has highlighted their heterogeneity and complexity. This review summarizes the recent findings for visceral adipose tissue CD4＋Foxp3＋ regulatory T cells （VAT Tregs）, muscle Tregs, bone Tregs and skin memory Tregs, with a focus on their unique functions in local tissues. This interpretation of the roles of tissue-specific Tregs and of their involvement in disease progression provides new insight into the discovery of potential therapeutic targets of human diseases.

How regulatory T cells sense and adapt to inflammation

The immune system exists in harmony and also with the potential for dynamic control in healthy individuals. Our healthy body needs to sense the presence of microbes and react through both innate and adaptive immunity to elim- inate infection. How our immune system senses the initiation, progression, and ter- mination of the inflammatory process is critical for maintaining immune home- ostasis. Thanks to the elegant experi- mental progress in using conditional knockout animal models, we have,