Immunopathology of rabies infection in mice selected for high or low acute inflammatory reaction

Rabies is a severe and lethal disease that produces a slight inflammatory response during the infection process. We analyzed the immunopathological mechanisms that occur in the central nervous system (CNS) using mice genetically selected for maximal or minimal acute inflammatory reaction (AIRmax or AIRmin). As viral samples, we adopted the antigenic variant 3 (AgV3) of rabies virus from hematophagous bats and a fixed virus strain (PV1 43/3). Titration of specific antibodies was performed using enzyme-linked immunosorbent assay (ELISA). We observed a slight increase in IgG and IgG1 isotypes in infected AIRmax mice. Incubation period, determined by intracerebral inoculation with 100 LD50, was 6-7 days for PV1 43/4 strain and 9-10 days for AgV3. No difference in viral replication was noticed between AIRmax and AIRmin mice. Mortality was 100 percent with both viral strains. Histopathological analysis of brains and spinal cords showed inflammatory foci in all regions of the CNS. No differences were noticed in the number of neutrophils. Negri bodies were observed in practically all sites analyzed. Results suggested that inflammatory reaction is not a determining factor in the susceptibility to rabies infection.

Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 ± 0.4 vs 0.3 ± 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 ± 0.3 vs 1.1 ± 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.