Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Chlamydia trachomatis Infection Control Programs: Lessons Learned and Implications for Vaccine Development

Chlamydia trachomatis control efforts that enhance detection and treatment of infected women may paradoxically increase susceptibility of the population to infection. Conversely, these surveillance programs lower incidences of adverse sequelae elicited by genital tract infection (e.g., pelvic inflammatory disease and ectopic pregnancy), suggesting enhanced identification and eradication of C. trachomatis simultaneously reduces pathogen-induced upper genital tract damage and abrogates formation of protective immune responses. In this paper, we detail findings from C. trachomatis infection control programs that increase our understanding of chlamydial immunoepidemiology and discuss their implications for prophylactic vaccine design

T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

Effective cancer immunotherapy requires overcoming immunosuppressive tumor microenvironments. We\ua0found that local nitric oxide (NO) production by tumor-infiltrating myeloid cells is important for adoptively transferred CD8(+) cytotoxic T\ua0cells to destroy tumors. These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Depletion of immunosuppressive, colony stimulating factor 1 receptor (CSF-1R)-dependent arginase 1(+) myeloid cells enhanced NO-dependent tumor killing. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors. Our results identify a network of pro-tumor factors that can be targeted to boost cancer immunotherapies

A decade of antimicrobial resistance in Staphylococcus aureus: A single center experience.

BackgroundThe emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) resulted in the recommended use of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for suspected S. aureus infections. The objective of this study was to determine the resistance to methicillin, clindamycin, and TMP-SMX in S. aureus isolates during a 10-year period.MethodsRetrospective review of the antimicrobial susceptibilities of all S. aureus isolates in the outpatient and inpatient settings at Nationwide Children's Hospital from 1/1/2005 to 12/31/2014. Duplicate isolates from the same site and year and those obtained for MRSA surveillance or from patients with cystic fibrosis were excluded.ResultsOf the 57,788 S. aureus isolates from 2005-2014, 40,795 (71%) were included. In the outpatient setting, methicillin resistance decreased from 54% to 44% (pConclusionIn a decade where >40,000 S. aureus isolates were identified at a large pediatric hospital, substantial changes in methicillin, clindamycin, and TMP-SMX resistance occurred. These findings highlight the importance of ongoing surveillance of the local antimicrobial resistance in S. aureus in order to guide empiric antimicrobial therapy

Síndrome de HELLP en el Hospital Nacional Guillermo Almenara Irigoyen: Presentación clínica y complicaciones de una emergencia obstétrica

Introdución: el síndrome de HELLP es una patología multisistémica caracterizada por hemólisis, enzimas hepáticas elevadas y trombocitopenia1, siendo considerada como una complicación de la preeclampsia severa. Objetivo: Determinar las características de las pacientes con Síndrome de HELLP del Hospital Guillermo Almenara Irigoyen entre los años 2005 y 2008. Material y método: Análisis retrospectivo de 45 historias clínicas de pacientes con Síndrome de HELLP. Resultados: El 71,1% (32/45) tenía edades entre los 20 y 35 años. Preeclampsia severa y aborto fueron los antecedentes obstétricos más frecuentes (33,33% y 26,7%, respectivamente). Se registró una hemoglobina mínima de 4,12mg/dL, un recuento plaquetario mínimo de 17 000 cel/mm3 y DHL máxima de 8 050 U/L. Las principales complicaciones reportadas fueron: Síndrome de Distress Respiratorio Agudo (14,0 y 31,11%) e Insuficiencia Renal Aguda (10,0 y 22,2%). El 26,7% (12/45) estuvo en Unidad de Cuidados Críticos (UCC) y se encontró diferencia significativa entre estas pacientes y las que no estuvieron en UCC, con respecto a la presencia de recuento plaquetario < 50 000 cel/mm3. (66,7% vs. 24,2%, p=0,009). 68,9% (31/45) fueron diagnosticadas durante la gestación y 30 pacientes de este grupo tuvieron parto por cesárea. La complicación neonatal más frecuente fue la prematuridad (80,6%). Se encontró diferencia entre las medias hemoglobina materna y el antecedente neonatal de depresión al nacer (8,15 ± 1,63 vs. 10,53 ± 2,44, p=0,007). Conclusiones: Los hallazgos muestran que el síndrome de HELLP conlleva a una alta morbilidad materna y neonatal, cuyo desenlace depende de un diagnóstico temprano y manejo oportuno