RRS1-R confers broad-spectrum resistance to several strains of the causal agent of bacterial wilt, Ralstonia solanacearum. Although genetically defined as recessive, this R gene encodes a protein whose structure combines the TIR-NBS-LRR domains found in several R proteins and a WRKY motif characteristic of some plant transcriptional factors and behaves as a dominant gene in transgenic susceptible plants. Here we show that PopP2, a R. solanacearum type III effector, which belongs to the YopJ͞AvrRxv protein family, is the avirulence protein recognized by RRS1-R. Furthermore, an interaction between PopP2 and both RRS1-R and RRS1-S, present in the resistant Nd-1 and susceptible Col-5 Arabidopsis thaliana ecotypes, respectively, was detected by using the yeast split-ubiquitin two-hybrid system. This interaction, which required the full-length R protein, was not observed between the RRS1 proteins and PopP1, another member of the YopJ͞AvrRxv family present in strain GMI1000 and that confers avirulence in Petunia. We further demonstrate that both the Avr protein and the RRS1 proteins colocalize in the nucleus and that the nuclear localization of the RRS1 proteins are dependent on the presence of PopP2. P lants rely on an innate immune response for their survival after pathogen attack. Specific recognitions between pathogen Avr and plant R proteins are crucial for the onset of the resistance response and determine the issue of many plantpathogen interactions by triggering plant defense. Disease results from the inactivation or absence of one or both partners (1). It has been postulated that R gene products are receptors for pathogen-encoded Avr components (2). Despite the cloning of numerous R and Avr genes, only two plant R proteins, Pto and Pi-ta, were shown to interact physically with their pathogen Avr counterparts, Avr-Pto and Avr-Pita, respectively, by using the yeast two-hybrid system (3-5). The hypothesis that R proteins are part of protein complexes was recently substantiated by the identification of multiprotein complexes including R and Avr proteins (6-9). Additionally, whereas Avr bacterial proteins expressed in plants carrying the cognate R protein generally induce a cell death program (10), termed the hypersensitive response, closely linked to resistance, they can also cause disease-like symptoms when expressed in plants lacking the appropriate R protein. Bacterial pathogenicity effectors such as Avr proteins are injected into the host cell via a type III secretion system (TTSS) (11). According to the guard model (9, 12), such effectors can associate and induce modifications of plant targets functioning as negative regulators of basal defense responses leading to disease development in plants lacking the corresponding R protein. In a resistant host, the plant target that interacts with both R and Avr proteins is guarded by the R protein, preventing its manipulation by pathogen effectors. The recent characterization of RIN4, a negative regulator of plant defense, strengthens this model (13).Most resistance p...

SUMMARY Mice lacking Junctional Adhesion Molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r-/-Rag1-/- mice to acute colitis. Although negligible contributions of adaptive immunity in F11r-/-Rag1-/- mice were observed, F11r-/-Rag1-/- mice exhibited increased microflora-dependent colitis. Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-β-producing CD4+ T cells in F11r-/- mice. Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4+ T cells and TGF-β. Absence of IgA in F11r+/+Igha-/- mice did not affect disease whereas F11r-/-Igha-/- mice displayed markedly increased susceptibility to acute injury induced colitis. These data establish a role for adaptive immune mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise.

Background Mycobacterium tuberculosis is an unusual pathogen, persisting for years in infected persons despite an immune response. Erythropoietin-producing hepatoma (Eph) receptors are critical for tissue organization. One hallmark of tuberculosis is the presence of granulomas consisting of organized immune cells. The importance of granuloma structure makes it likely that Eph receptors play a role in immunity to tuberculosis. Methods We infected mice with low doses of M. tuberculosis by the aerosol method and examined the effects on ephA gene expression, pathology, composition of lymphocytes in the lungs (by flow cytometry), migration of CD4+ and CD8+ T cells, and numbers of cytokine-expressing cells. Results Mice infected with M. tuberculosis displayed higher expression of ephA1 and ephA2 as well as ephrinA1, which encodes the ligand for EphA1 and EphA2. Interestingly, ephA2−/− mice displayed greater pathology, greater accumulation of T cells and dendritic cells, and higher levels of proinflammatory cytokines than did normal C57BL/6 mice. Furthermore, T cells from ephA2−/− mice migrated more efficiently than did those from C57BL/6 mice. Conclusions These observations suggest that ephA-related genes may provide a mechanism that M. tuberculosis uses to circumvent the host response, given that accumulation of T cells appears to be due to the inhibition of immune cell migration by EphA2. Ultimately, the absence of ephA2 results in greater clearance of M. tuberculosis during the chronic phase of infection, suggesting that induction of ephA2 is important for the survival of M. tuberculosis during latency.

Mice lacking Junctional Adhesion Molecule A (JAM‐A) exhibit enhanced intestinal permeability, bacterial translocation, and elevated numbers of colonic T and B cells and IgA, yet do not develop colitic disease. To study whether enhanced adaptive immunity compensates for increased intestinal permeability, we examined susceptibility of Jam‐a−/−Rag−/− mice to acute, injury‐induced colitis. Data revealed negligible contribution of adaptive immunity in mice with intact epithelial barriers; however Jam‐a−/− Rag−/− mice exhibited dramatically increased microflora‐dependent colitis compared to Jam‐a−/− controls. Specific depletion of T cells and neutralization of TGFβ revealed a protective role for TGFβ‐producing CD4 T cells in Jam‐a−/− but not Jam‐a+/+ mice. A major mechanism of TGFβ‐producing CD4 T cell‐mediated protection was via increased IgA production and consistent with this observation, Jam‐a−/−Iga−/− mice displayed markedly increased colitis. These data delineate a critical protective pathway involving TGFβ‐producing CD4 T cell‐induced IgA in response to epithelial barrier defects and mucosal injury‐induced intestinal inflammation. These findings suggest that, under conditions of preexisting intestinal barrier compromise, adaptive immune mechanisms play an important compensatory role that protects from colitis. This work is supported by NIH grants DK061379, DK59888 and AA017870.

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