Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (TH1)-TH17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor.

Irf5 promotes inflammatory macrophage polarization and th1/th17 response

The ambiguity of play

Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after "recovery" from acute events As so many sepsis survivors succumb later to persistent, recurrent, nosocomial, and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long-term patient outcomes These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality

The immune system's role in sepsis progression, resolution, and long‐term outcome

Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is often used to treat leucopenia. Other haematopoietins may increase the number of circulating leucocytes with higher efficiency, but GM-CSF has additional effects that may be far more relevant than its haematopoietic activity. GM-CSF induces differentiation, proliferation and activation of macrophages and dendritic cells which are necessary for the subsequent T helper cell type 1 and cytotoxic T lymphocyte activation. GM-CSF haematopoietic and non-haematopoietic functions have pro-inflammatory and immune regulatory potential to treat a variety of autoimmune diseases and tumours. On the other hand, GM-CSF deficiency leads to various immune dysfunctions and the current utilization of GM-CSF as haematopoietic factor might be an accurate but very incomplete indication for a cytokine with vast clinical potential.

Granulocyte–macrophage colony-stimulating factor: not just another haematopoietic growth factor

B-chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal B cells, which may be the result of several factors leading to extended B-CLL cell lifespan, increased proliferative capacity and diminished cell death. Here we review the implications of several signals mediated by receptors, such as surface IgM, CD6 and CD40, for the B-CLL cell survival, together with data on gene modulation in relation to the apoptosis process in B-CLL cells. We also describe some features of the Fas/FasL system in B-CLL that hypothetically might contribute to the accumulation of leukaemic cells and the progression of the disease, by downregulating the apoptotic response or avoiding the autologous immune response.

Apoptosis in B-chronic lymphocytic leukaemia

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10(6) splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.

Induction and treatment of anergy in murine leprosy.

Antibiotic-resistant Escherichia coli are common causative agents of human urinary tract infections. Organotin compounds (OTCs) are man-made chemicals that may affect the renal function of exposed humans and rodents. OTCs are widely recognized as bactericides. However, many environmental and a few clinically relevant bacteria have been found resistant to high concentrations of some OTCs. We examined the susceptibility from 47 E. coli clinical isolates to 12 antibiotics and 5 OTCs. Minimum inhibitory concentrations were determined by the fully automated Sensititre™ ARIS™ 2X system, and E. coli strains were classified as resistant, intermediate resistant, or sensitive, according to the M07-A10 and M100-S26 criteria from the National Committee for Clinical Laboratory Standards. All 47 E. coli strains were susceptible to amikacin but resistant to imipenem and intermediate resistant to ampicillin, cefuroxime, and chloramphenicol. In addition, 26 strains were resistant and 21 intermediate resistant to aztreonam, 24 strains were resistant and 23 intermediate resistant to ceftazidime, 44 strains were intermediate resistant and 3 sensitive to cephalothin, and 43 strains were intermediate resistant and 4 sensitive to ciprofloxacin. Approximately half of the strains were susceptible to cefepime, cefotaxime, and gentamicin. E. coli strains were also found resistant to triphenyltin, tributyltin, dibutyltin, trimethyltin, or dimethyltin at final concentration between 10 μmol/L and 1 mmol/L, during 72-h in vitro culture. However, higher in vitro growth inhibition was induced by these OTCs in the presence of the efflux pump inhibitor carbonyl cyanide-m-chlorophenyl hydrazone, which suggests that efflux pumps contribute to making antibiotic-resistant E. coli also resistant to OTCs.

Clinical isolates of Escherichia coli are resistant both to antibiotics and organotin compounds.

Organotin compounds are man-made chemicals used worldwide for diverse applications. These organometallic compounds may be released from antifouling paints, polyvinyl chloride and other materials into terrestrial and aquatic environments. Mexico City is a highly populated and industrialized city with many potential sources of environmental pollution. We evaluated the content of butyltins, triphenyltin and bacteria in water from various sites with different water quality in Mexico City, Pachuca City and two towns located between these two cities. Butyltins and/or triphenyltin were detected by gas chromatography and mass spectrometry analysis in samples from 4/4 sites containing wastewater, 1/2 sites containing reclaimed water and 2/5 sites holding accumulated water in open-air deposits. Neither organotin compounds nor bacteria were found in household water samples. However, 80 bacterial strains were isolated from partially treated or untreated wastewater and 72 of them were identified at the genus a...

M. Aguilar-Santelises

Papers

Granulocyte–macrophage colony-stimulating factor: not just another haematopoietic growth factor

Apoptosis in B-chronic lymphocytic leukaemia

Induction and treatment of anergy in murine leprosy.

Clinical isolates of Escherichia coli are resistant both to antibiotics and organotin compounds.

Wastewater from Mexico City contains organotin compounds and organotin-resistant bacteria