Human neutrophils produce IL-12, IL-10, PGE2 and LTB4 in response to Paracoccidioides brasiliensis. Involvement of TLR2, mannose receptor and dectin-1.

The functions of phagocytic cells against pathogens are initiated by the interaction between membrane receptors and molecular structures which compose the cell wall of these microorganisms. Thus our study aimed to identify the neutrophil receptors involved in the recognition of different strains of Paracoccidioides brasiliensis and the consequent modulation of immune response through the production of cytokines and inflammatory mediators. Neutrophils did not produce TNF-alfa in response to both strains. However, these cells produce IL-12, mainly in response to Pb 265, with participation of TLR2 and dectin-1. These cells also produce L-10, whose levels were higher for Pb 18 with involvement of TLR2 and MR and only TLR2 for Pb 265. The production of PGE2 and LTB4 was detected similarly for the two strains. For PGE2, MR and dectin-1 were involved, while in relation to LTB4, none of them. In summary, we demonstrated that neutrophils have a dynamic role during host immune response to P. brasiliensis, since in addition to their role as effector cells of innate immunity; they have the capacity to modulate innate and adaptative immune response against this fungus by producing cytokines and lipidic mediators. This modulation may be toward a pró- or anti-inflammatory pattern in a dependence of P. brasiliensis strains and PRR involved in fungus recognition by these cells.

The role of leukotriene B4 in early stages of experimental paracoccidioidomycosis induced in phenotypically selected mouse strains.

Paracoccidioidomycosis is a human systemic mycosis caused by the fungus Paracoccidioides brasiliensis. The mechanisms involved in innate immune response to this fungus are not fully elucidated. Leukotrienes are known to be critical for the clearance of various microorganisms, mainly by mediating the microbicidal function of phagocytes. We investigated the involvement of leukotriene B4 in the early stages of experimental paracoccidioidomycosis, which was induced by intratracheal inoculation of the fungus in selected mouse lines. The mouse lines utilized were produced through bi-directional phenotypic selection, endowed with maximal or minimal acute inflammatory reactivity, and designated AIRmax and AIRmin, respectively. AIRmax mice were more resistant to the infection, which was demonstrated by reduced lung fungal loads. However, the two lines produced similar amounts of leukotriene B4, and pharmacological inhibition of this mediator provoked similar fungal load increases in the two lines. The lower fungal load in the AIRmax mice was associated with a more effective inflammatory response, which was characterized by enhanced recruitment and activation of phagocytic cells and an increased production of activator cytokines. This process resulted in an increased release of fungicidal molecules and a diminution of fungal load. In both lines, leukotriene production was associated with a protective response in the lung that was consequent to the effect of this eicosanoid on the influx and activation of phagocytes.

Surtos de infecção por Piscinoodinium pillulare e Henneguya spp. em pacus (Piaractus mesopotamicus) criados intensivamente no Sudoeste de Goiás / Outbreaks of Piscinoodinium pillulare and Henneguya spp. infection in intensively raised Piaractus mesopotamicus in Southwestern Goiás, Brazil

Três surtos de infecção por Piscinoodinium pillulare e Henneguya spp. em Piaractus mesopotamicus criados intensivamente no Sudoeste de Goiás são descritos. Dois surtos ocorreram no inverno e um no verão. As taxas de morbidade (58,57%-90%) e mortalidade (100%) foram determinadas. Episódios de estresse ocorreram previamente em todos os casos. Sinais clínicos incluíam mudanças comportamentais e movimentos erráticos com perda de equilíbrio. Os principais achados macroscópicos foram tumefação das brânquias com exsudato mucoso esbranquiçado. Microscopicamente, as brânquias apresentaram inflamação linfoplasmocítica e necrosante, multifocal, leve a moderada, com hipertrofia e fusão de lamelas secundárias. Adicionalmente, numerosos trofontes intralesionais de P. pillulare e cistos de Henneguya spp. foram notados. Para o conhecimento dos autores, essa parece ser a primeira descrição de infecção por P. pillulare e Henneguya spp. em peixes criados no Sudoeste de Goiás.

Three outbreaks of infection by Piscinoodinium pillulare and Henneguya spp. in Piarac tus mesopotamicus intensively raised in Southwestern Goiás, Brazil, are described. Two outbreaks occurred in the winter and another one in summer. Morbidity (58.57%-90%) and mortality (100%) rates were determined. Stress episodes occurred previously in all cases. Clinical signs included behavior changes and erratic movements with loss of equilibrium. Main gross findings were swelling of the gills with white mucus exudate. Microscopically, gills had mild to moderate multifocal necrotizing and lympho-plasmocytic inflammation with hypertrophy and fusion of secondary lamellae. In addition, numerous intralesional trophonts of P. pillulare and cysts of Henneguya spp. were noted. According to our knowledge, this seems to be the first description of Piscinoodinium pillulare e Henneguya spp. infection in fishes reared in Southwestern Goiás, Brazil.

Immune response to the Rhodococcus equi infection in high and low antibody-producing mice (Selection IV-A).

Rhodococcus equi is a gram-positive, facultative intracellular bacterium which infects macrophages and causes rhodococcal pneumonia and enteritis in foals. Recently, this agent has been recognized as an opportunistic pathogen for immunocompromised humans. Several murine experimental models have been used to study R. equi infection. High (H(IV-A)) and Low (L(IV-A)) antibody (Ab)-producers mice were obtained by bi-directional genetic selections for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). These lines maintain their phenotypes of high and low responders also for other antigens than those of selection (multispecific effect). A higher macrophage activity in L(IV-A) mice has been described for several intracellular infectious agents, which could be responsible for their intense macrophage antigens (Ag)-handling and low Ab production. Due to these differences, L(IV-A) mice were found to exhibit a better performance to trigger an effective immune response towards intracellular pathogens. The objective of this work was to characterize the immune response of Selection IV-A against R. equi. H(IV-A) and L(IV-A) mice were infected with 2.0x10(6) CFU of ATCC 33701+R. equi by intravenous route. With regards to bacterial clearance and survival assays, L(IV-A) mice were more resistant than H(IV-A) mice to virulent R. equi. L(IV-A) mice presented a higher hydrogen peroxide (H2O2) and nitric oxide (NO) endogenous production by splenic macrophages than H(IV-A) mice. L(IV-A) expressed the most intense cellular response, available by the Delayed-Type Hypersensitivity (DTH) reaction, which activated macrophages and produced more H2O2 and NO. The three times higher specific antibodies titres in H(IV-A) indicated that Selection IV-A maintained the multispecific effect and the polygenic control of humoral and cellular responses also to R. equi.