Rabies in small animals.

Rabies in small animals has been dramatically reduced in the United States since the introduction of rabies vaccination of domestic animals in the 1940s. As a consequence, the number of human rabies cases has declined to only a couple per year. During the past several years, the dog rabies variant has almost disappeared completely. Rabies in wildlife has skyrocketed, however. Each wildlife species carries its own rabies variant(s). These wildlife epizootics present a constant public health threat in addition to the danger of reintroducing rabies to domestic animals. Vaccination is the key to prevent rabies in small animals and rabies transmission to human beings.

Role of chemokines in the enhancement of BBB permeability and inflammatory infiltration after rabies virus infection.

Induction of innate immunity, particularly through the induction of interferon and chemokines, by rabies virus (RABV) infection has been reported to be inversely correlated with pathogenicity. To further investigate the association between the expression of chemokines and RABV infection, laboratory-attenuated RABV (B2C) and wild-type (wt) RABV (DRV) were administered to Balb/c mice intramuscularly. Chemokine expression, inflammatory cell infiltration, and blood-brain barrier (BBB) permeability were evaluated at various time points after infection. At day 3 post-infection (p.i.) there was very little inflammation in the central nervous system (CNS) and BBB permeability did not change in mice infected with either virus when compared with mock-infected mice. At 6 day p.i., infection with B2C induced the expression of inflammatory chemokines and infiltration of inflammatory cells into the CNS, while these changes were minimal in DRV-infected mice. Furthermore, infection with B2C significantly enhanced BBB permeability comparing to infection with DRV. Among the upregulated chemokines, the expression of IP-10 was best correlated with infiltration of inflammatory cells into the CNS and enhancement of BBB permeability. These data indicate that laboratory-attenuated RABV induces expression of chemokines and infiltration of inflammatory cells into the CNS. Upregulation of chemokines by B2C may have triggered the change in BBB permeability, which helps infiltration of inflammatory cells into the CNS, and thus attenuation of RABV.

Cellular expression and antimicrobial function of a phylogenetically conserved novel histone 1x-like protein on mouse cells: a potential new class of pattern recognition receptor.

A H1x-like protein (i.e., NCAMP-1) is expressed on the membrane and in GEs from fish NK-like cells. In the present study, we identify the imprinting control region mouse NCAMP-1 ortholog using NCAMP-1 polyclonal antibodies and mAb. Polychromatic flow cytometry revealed NCAMP-1 expression on PBLs (Gr-1(+) PMNs were 21.1% NCAMP-1(+); DX-5(+) NK cells were 12.2% NCAMP-1(+)), mesenteric LN cells (CD11c(+) DCs were 23.2% NCAMP-1(+); Gr-1(+) PMNs were 24.8% NCAMP-1(+); CD21(+) B cells were 17.8% NCAMP-1(+)), and splenocytes (CD11c(+) were 39.6% NCAMP-1(+); Gr-1(+) PMNs were 40.9% NCAMP-1(+); DX-5(+) NK cells were 24.3% NCAMP-1(+); CD21(+) B cells were 28.5% NCAMP-1(+)). Western blot analysis using pNCAMP-1 and GEs from RAW 264.7 cells produced a 32-kDa signal. GEs from RAW 264.7 cells produced a significant reduction in Escherichia coli CFU. This antimicrobial killing activity was inhibited by pretreatment of the extract with (polyclonal) anti-NCAMP-1. Treatment with preimmune serum did not reduce bacterial cell killing. Confocal microscopy using NCAMP-1 and LAMP-1 mAb demonstrated that NCAMP-1 was located on the membrane and in cytosolic vesicles of RAW 264.7 cells and did not appear to colocalize with LAMP-1. NCAMP-1 may participate as a bifunctional protein on cells. It is expressed on the membranes of phagocytic cells, NK cells, and APCs in mice as well as in the granules of macrophages. In phagocytic cells, NCAMP-1 may participate in a nonregulated exocytosis pathway of cellular secretion.