Traffic of leukocytes and cytokine up-regulation in the central nervous system in sepsis (original) (raw)
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Cellular and humoral immune responses during intrathoracic paracoccidioidomycosis in BALB/c mice
Comparative Immunology, Microbiology and Infectious Diseases, 2009
Paracoccidioidomycosis is a chronic infection that primarily affects the lungs. Here we investigated cellular and humoral immune responses after intrathoracic Paracoccidioides brasiliensis infection in BALB/c mice. P. brasiliensis-colony-forming units (CFUs), fungal DNA and granulomas in lungs increased progressively, peaking at day 90 postinfection (p.i.). IFN-g production was highest on day 15 p.i., declining thereafter. The kinetics of the NO production was similar to that described for IFN-g. In contrast, IL-10 increased from day 45 p.i. reaching a peak at day 90. Levels of serum IgG1 were higher than IgG2a between days 30 and 90 p.i. 30% of mice died by day 90 p.i. These data indicate that infection with P. brasiliensis by the intrathoracic route shows high IFN-g and NO production at day 15 p.i., unable to control multiplication of fungi, which appears to be associated with a progressive increase in IL-10 and in the number and complexity of granulomas. # .br (A.P. Ferreira).
Development of a Murine Model of Neuroparacoccidioidomycosis
Journal of Neuroparasitology, 2010
Paracoccidioidomycosis is the most important systemic mycosis in Latin America. In the last decades, it was verified that central nervous system involvement is frequent, occurring in 12.5% of the cases. Despite the relevance of this severe form of the disease, there are not experimental models for the study of the interactions established between the fungus and the central nervous system. We developed a murine model of neuroparacoccidioidomycosis with intracranial inoculation of 10 6 yeast cells of Paracoccidioides brasiliensis (strain PB18) in C57BL/6 mice. Animals developed lesions similar to those described in human patients and morbidity was evaluated by the SHIRPA behavioral battery, showing progressive and severe cognitive compromise. With the development of this model, future studies will be able to evaluate several pathogenic and therapeutic aspects of neuroparacoccidioidomycosis in order to improve survival or lessen morbidity of this severe disease.
Clinical & Experimental Immunology, 1995
In an attempt to understand better the immunoregulatory disorders in paracoccidioidomycosis (PCM), the possible correlation between interleukin pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody levels was investigated in the polarized clinical forms of this disease. We studied 16 PCM patients, eight with the disseminated disease (four under treatment and four non-treated) and eight with the chronic disease. The patients with disseminated disease exhibited high antibody titres specific to Paracoccididoides brasiliensis antigen compared with patients with the chronic form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of non-treated disseminated PCM patients were increased, which correlated positively with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA) (P<0-01) and with the high antibody titres (P<00001) of these patients. Moreover, we found in the disseminated PCM patients positive correlations between IL-1 and IL-6 (P=00007); IL-1 and TNF (P=0-0045); IL-1 and IL-6 with the high antibody titres (P = 0-0834 and P = 0-0631, respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations were found with those interleukins in the treated disseminated and chronic patients or in controls. It was interesting to find an inverse correlation between IL-4 and antibody production in non-treated disseminated PCM (r =-0 4770); moreover, a significant correlation (P = 0-0820) was found in chronic PCM patients with respect to the low level of either IL-4 and antibody titres against fungus antigen. Chronic PCM patients also had IL-2 levels inversely correlated with antibody production (r =-0-6313; P = 0-0628). Inverse correlations were also observed between IL-2 and IL-6 levels in non-treated disseminated patients (P = 0 0501) and between IL-2 and IL-4 in chronic patients (P=0-013 1). The inflammatory cytokines might have a pivotal role in the genesis and in control of some aspects of the disease, such as granulomatous reaction, hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.
Proceedings of the National Academy of Sciences, 1999
The pathogenesis of tuberculous meningitis, a devastating complication of tuberculosis in man, is poorly understood. We previously reported that rabbits with experimental tuberculous meningitis were protected from death by a combination of antibiotics and thalidomide therapy. Survival was associated with inhibition of tumor necrosis factor ␣ (TNF-␣) production by thalidomide. To test whether cerebrospinal f luid (CSF) levels of TNF-␣ correlated with pathogenesis, the response of rabbits infected in the central nervous system (CNS) with various mycobacterial strains was studied.
Clinical and Experimental Immunology, 2008
The dissemination of Paracoccidioides brasiliensis cells to the heart, omentum/pancreas, spleen, liver and lungs, assessed by colony forming unit (CFU) counts, the levels of specific antibodies to this fungal agent (by ELISA), and the specific DTH reaction were studied in susceptible (B10.A) and resistant (A/Sn) mice. The animals were infected intraperitoneally with P. brasiliensis yeast cells and were evaluated 2, 4, 12 and 16 weeks later. The mosl remarkable differences between the two mouse strains were observed 16 weeks after infection, when B10.A mice displayed high numbers ofCFU in all examined organs, except the heart, high antibody titres, and depressed DTH response. At this point. A/Sn mice presented low or absent CFU in all organs, low antibody litres and expressive DTH response. The CFU counts were shown to be a reliable parameter to discriminate susceptible from resistant animals. The fungal load in the most affected organs correlated wilh the antibody litres and was inversely correlated with the intensity of the DTH reaction. The patterns of immune response in this model mimic human paracoccidioidomycosis, in which high specific antibody levels and depressed DTH reactions are found in multifocal and severe forms of the disease.
Proceedings of the National Academy of Sciences, 1999
The pathogenesis of tuberculous meningitis, a devastating complication of tuberculosis in man, is poorly understood. We previously reported that rabbits with experimental tuberculous meningitis were protected from death by a combination of antibiotics and thalidomide therapy. Survival was associated with inhibition of tumor necrosis factor α (TNF-α) production by thalidomide. To test whether cerebrospinal fluid (CSF) levels of TNF-α correlated with pathogenesis, the response of rabbits infected in the central nervous system (CNS) with various mycobacterial strains was studied. CNS infection with Mycobacterium bovis Ravenel, M. bovis bacillus Calmette–Guérin (BCG) Pasteur, and M. bovis BCG Montreal were compared. M. bovis Ravenel induced the highest levels of TNF-α in the CSF in association with high leukocytosis, protein accumulation, and severe meningeal inflammation. BCG Pasteur had intermediate effects, and BCG Montreal was the least virulent. In addition, M. bovis Ravenel number...
Medical Mycology, 2000
Cellular immunity is usually suppressed during paracoccidioidomycosis (PCM) and is restored after treatment. In this study we evaluated the induction of a type 1 (interferon gamma (IFN-g)), a type 2 (interleukin (IL)-10) and a primarily macrophage derived cytokine (tumor necrosis factor (TNF)-a) in peripheral blood mononuclear cells (PBMC) from patients with PCM. Eight male patients with active PCM, nine male patients with clinical remission of the disease and 10 healthy control subjects were enrolled in the study. Cytokines were induced with non-speci c stimuli-phytohaemagglutin (PHA) (induces IL-10 and IFN-g), Lipopolysaccharide (induces TNF-a)-and Paracoccidioides brasiliensis antigen (PbAg) (induces IL-10, IFN-g and TNF-a). Induction of IFN-g with PHA differed among the three groups (P B 0•01; Kruskal-Wallis test) and with PbAg was lower in patients with active disease compared to those in clinical remission (P ¾ 0•05; Mann-Whitney). Induction of IL-10 and of TNF-a was similar in the three groups. The suppressed production of IFN-g in patients with active disease may underscore the cellular immune de ciency seen in these patients.
Journal of Clinical Microbiology, 2005
Neuroparacoccidioidomycosis (neuroPCM) is the central nervous system infection by the fungus Paracoccidioides brasiliensis . Its diagnosis is a difficult task that depends on neuroimaging techniques such as computed tomography and magnetic resonance imaging. However, the detection of circulating P. brasiliensis antigens in body fluids by inhibition enzyme-linked immunosorbent assay (inh-ELISA) has provided encouraging results. In this study, 14 cerebrospinal fluid (CSF) and 11 serum samples of patients with neuroPCM were analyzed by inh-ELISA for detection of circulating glycoprotein antigens of 43 kDa (gp43) and 70 kDa (gp70). Circulating gp43 and gp70 antigens were detected in all CSF samples from patients with neuroPCM at mean concentrations of 19.3 and 6.8 μg/ml, respectively. In addition, both gp43 and gp70 antigens were detected in 10 of 11 serum samples analyzed at mean concentrations of 4.6 and 4.0 μg/ml, respectively. By immunodiffusion test, CSF samples were determined to ...