Human Anti-Mouse IFNGR1 monoclonal Antibody, clone SFB290 [APC]

Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused byParacoccidioidesspp. This mycosis has been associated with high morbidity and sequels, and its clinical manifestations depend on the virulence of the infecting strain, the degree and type of immune response, infected tissues, and intrinsic characteristics of the host. The T helper(Th)1 and Th17/Th22 cells are related to resistance and control of infection, and a Th2/Th9 response is associated with disease susceptibility. In this study, we focused on interleukin(IL)-12p35 (IL12A), IL-18 (IL18), and IFN-gamma receptor 1 (IFNGR1) genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyzeIL12A-504 G/T (rs2243115),IL18-607 C/A (rs1946518), andIFNGR1-611 A/G (rs1327474) single nucleotide polymorphisms (SNP). One hundred forty-nine patients with the acute form (AF), multifocal chronic (MC), or unifocal chronic (UC) forms of PCM and 110 non-PCM individuals as a control group were included. In the unconditional logistic regression analysis adjusted by ethnicity and sex, we observed a high risk of theIL18-607A-allele for both AF [p= 0.015; OR = 3.10 (95% CI: 1.24-7.77)] and MC groups [p= 0.023; OR = 2.61 (95% CI: 1.14-5.96)] when compared with UC. TheIL18-607A-allele associated risk for the AF and MC groups as well as the protective role of theC-allele in UC are possibly linked to higher levels of IL-18 at different periods of the course of the disease. Therefore, a novel role ofIL18-607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM.

Apparently for the first time, the peripheral blood monocytes of individuals with active visceral leishmaniasis (VL) have been found to show reduced expression of interferon gamma receptor-1 (IFNGR1). Since interferon gamma is the main cytokine responsible for defence against leishmanial parasites, it was thought possible that effective antileishmanial drugs may up-regulate IFNGR1. Confocal microscopy confirmed that monocytes from VL patients who had been treated, with sodium antimony gluconate (SAG), did display IFNGR1 up-regulation. To see if this effect could be mimicked in vitro, IFNGR1 expression was investigated using a human macrophage cell line (THP1), northern blotting and confocal microscopy. When the THP1 cells were treated with SAG or pentamidine, their expression of the receptor was increased. This drug-induced up-regulation was more intense if the macrophages were infected with Leishmania donovani than if they were left uninfected. The possibility that at least some antileishmanial drugs act by up-regulating IFNGR1 expression needs to be explored further. A good model for investigating the mechanisms of action of antileishmanial drugs might be based on the THP1 cell line.