Role of macrophage migration inhibitory factor in the Th2 immune response to epicutaneous sensitization.

We examined the role of macrophage migration inhibitory factor (MIF) in the generation of the Th2 response using MIF-deficient mice in a model of epicutaneous sensitization to ovalbumin. Lymph node cells from sensitized MIF-deficient mice produce lower levels of Th2 cytokines after antigen challenge when compared to their wild-type counterparts. Sensitized mice lacking MIF show less pulmonary inflammation after intranasal antigen exposure. Mice deficient in CD74, the MIF receptor, also are unable to generate an inflammatory response to epicutaneous sensitization. Examination of the elicitation phase of the atopic response using DO11.10 OVA TCR transgenic animals shows that T cell proliferation and IL-2 production are strongly impaired in MIF-deficient T cells. This defect is most profound when both T cells and antigen-presenting cells are lacking MIF. These data suggest that MIF is crucial both for the sensitization and the elicitation phases of a Th2-type immune response in allergic disease.

Fibrillar IgA deposition in dermatitis herpetiformis--an underreported pattern with potential clinical significance.

Dermatitis herpetiformis has characteristic clinical and histopathologic findings. A fibrillar pattern of IgA deposition on direct immunofluorescence in dermatitis herpetiformis is underreported. Here, we describe three patients with the fibrillar pattern of IgA deposition on direct immunofluorescence examination that initially misled diagnosis in one of the three. Interestingly, two of the three patients lacked anti-transglutaminase and anti-endomysial antibodies but had a clinical course typical of dermatitis herpetiformis. Dermatitis herpetiformis may have a fibrillar rather than granular pattern of IgA deposition on direct immunofluorescent microscopy, and patients with this pattern of immunoglobulin deposition may lack circulating autoantibodies.

The ShiA protein encoded by the Shigella flexneri SHI-2 pathogenicity island attenuates inflammation.

Shigella spp. are the aetiologic agents of dysentery, a severe diarrhoeal syndrome characterized by acute inflammation in the colon. The inflammatory response, which includes recruitment of polymorphonuclear leukocytes (PMN), damages the colonic mucosa and exacerbates the infection. Shigella encodes a pathogenicity island (PAI), SHI-2, which is localized in a region of the chromosome linked to the induction of inflammation. Surprisingly, SHI-2 deletion mutants induce a stronger inflammatory response than wild-type Shigella as measured by increased villus blunting, increased PMN infiltration and induction of apoptosis in a rabbit ileal loop model of shigellosis. Mutational analysis mapped the hyper-inflammatory phenotype to a single gene, shiA. Similar to SHI-2 deletion mutants, infection with a shiA mutant strain induces dramatically elevated levels of inflammation when compared to the wild-type strain. Furthermore, infection with a wild-type strain containing multiple copies of shiA results in fewer infiltrating PMN and apoptotic cells, as well as preservation of a normal villus architecture at the site of infection, thus acting in a dominant fashion over the pro-inflammatory mechanisms of Shigella. The molecular mechanism of action of ShiA is independent of any in vitro phenotype associated with Shigella virulence. Our data suggest that ShiA allows Shigella to attenuate the host inflammatory response in a novel manner.