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Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales. Recipients of the gut microbiota from helminth-infected wide-type, but not STAT6-deficient, Balb/c donors had increased fecal pathogen shedding and significant worsening of Citrobacter-induced colitis compared to recipients of microbiota from control donors. Recipients of helminth-altered microbiota also displayed increased regulatory T cells and IL-10 expression. Depletion of CD4+CD25+T cells and neutralization of IL-10 in recipients of helminth-altered microbiota led to reduced stool C. rodentium numbers and attenuated colitis. These results indicate that alteration of the gut microbiota is a significant contributor to the H. polygyrus-induced exacerbation of C. rodentium colitis. The helminth-induced alteration of the microbiota is Th2-dependent and acts by promoting regulatory T cells that suppress protective responses to bacterial enteropathogens.

Infection with the intestinal helminth parasite Heligmosomoides polygyrusexacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrusresulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetesand decreases in Firmicutesand Lactobacillales. Recipients of the gut microbiota from helminth-infected wide-type, but not STAT6-deficient, Balb/c donors had increased fecal pathogen shedding and significant worsening of Citrobacter-induced colitis compared to recipients of microbiota from control donors. Recipients of helminth-altered microbiota also displayed increased regulatory T cells and IL-10 expression. Depletion of CD4+CD25+T cells and neutralization of IL-10 in recipients of helminth-altered microbiota led to reduced stool C. rodentiumnumbers and attenuated colitis. These results indicate that alteration of the gut microbiota is a significant contributor to the H. polygyrus-induced exacerbation of C. rodentiumcolitis. The helminth-induced alteration of the microbiota is Th2-dependent and acts by promoting regulatory T cells that suppress protective responses to bacterial enteropathogens.

When Salmonella enterica invades mammalian cells, it activates signals leading to increased expression of inflammatory mediators. One such mediator is nitric oxide (NO), which is produced under control of the enzyme inducible NO synthase (iNOS). Induction of iNOS in response to Salmonella infection has been demonstrated, but the bacterial effector molecules that regulate expression of the enzyme have not been identified. In the study reported here, an analysis of Salmonella-dependent iNOS expression in macrophages was carried out. Wild-type Salmonella strains increased the levels of both iNOS protein and mRNA in murine macrophage cell lines in an invasion-independent fashion. Mutant strains lacking a functional pathogenicity island 1-encoded type III secretion system, as well as strains lacking the invasins SipB, SipC, and SipD, were impaired in iNOS induction. Complementation experiments indicated that all three of the invasins were required for induction of iNOS expression. These results suggested that an effector protein, translocated into macrophages via the type III secretion system in a SipB-, SipC-, and SipD-dependent manner, might be the ultimate mediator of iNOS induction. In keeping with this idea, a mutant strain deficient in SopE2, a recently described homolog of SopE, was found to be impaired in the induction of iNOS expression. These observations suggest that iNOS expression is regulated by signals activated by SopE2 (and possibly SopE) and that the role of SipB, SipC, and SipD in this process is to facilitate translocation of the relevant effector.

Vibrational lifetime and spectral shift data for the asymmetric CO stretching mode of W(CO)6 in supercritical ethane, carbon dioxide, and fluoroform as a function of density at two temperatures are presented, and the lifetime (T1) measurements are compared to theory. The data and theory are refinements of previous work. Measurements at zero density allow the contribution from solute−solvent interactions to be separated from strictly intramolecular contributions to T1. The results in the polyatomic SCFs are compared to data in Ar. The density functional/thermodynamic theory¹ has been extended to include contributions at large wavevector (k). Very good, quantitative agreement between theory and data taken in ethane and fluoroform is achieved, but the agreement for data taken in carbon dioxide, while reasonable, is not as good. The theory uses a variety of input information on the SCF properties obtained from the fluids' equations of state and other tabulated thermodynamic data. The solute−solvent spatial distribution is described in terms of hard spheres. The theory is able to reproduce the data without solute−solvent attractive interactions or clustering in the calculation of the spatial distribution.

Concurrent events in photoelecron spectroscopy such as photoionisation, shake-up and shake-off transitions are studied using atomic wavefunctions recently developed by one of the authors and the concept of the Slater transition state. Various transition energies and intensities are calculated to test the efficiency of the wave-functions and the applicability of the transition state method to these processes. It is concluded that the method is reliable enough to be useful in the assignment of these transitions in the experimental spectrum.

The thermodynamic temperature variable appropriate for the description of the scaling behavior of chain dimensions R and density correlations ξ in polymer solutions in the critical through mean field limits is identified by setting up and solving the renormalization group (RG) equation for the system. The solution to the RG equation is obtained by expressing the set of renormalization constants that relate the bare parameters of the Hamiltonian to their renormalized counterparts as approximate resummed expansions in the coupling constants of the system. These expansions, which include unknown coefficients, are so defined that certain calculated asymptotic limits of R and ξ are reproduced. In satisfying these matching conditions, the unknown coefficients are determined self-consistently; they in turn fix the form of the relevant crossover variable. The predicted measure of distance to the critical temperature is found in this way to coincide with de Gennes's original proposal. This semiempirical approach to the calculation of asymptotic and crossover behavior in polymer solutions provides a more rigorous alternative to simple scaling prescriptions but eschews the elaborate mathematical machinery of field-theoretic methods.

A cDNA encoding the Mac-2 antigen, a surface marker highly expressed by thioglycollate-elicited macrophages, has been cloned by immunoscreening of a lambda gt11-P388D1 expression library. The nucleotide sequence of the cDNA is identical to that of carbohydrate-binding protein 35, a galactose-specific lectin found in fibroblasts and highly homologous to a rat IgE-binding protein from basophilic leukemia cells. The in vitro synthesized Mac-2 protein displayed the expected carbohydrate- and IgE-binding properties. By pulse-chase analysis and subcellular fractionation studies, the Mac-2 protein was found in the cytosol but was also seen to accumulate in the extracellular medium. The latter finding was surprising in view of the fact that the cDNA did not encode a signal peptide or transmembrane domain. An alternatively spliced cDNA with the potential to encode a NH2 terminally extended Mac-2 protein with a stretch of hydrophobic amino acids at its NH2 terminus was also found, but it is not clear whether it is the source of the extracellular Mac-2. Possible functions for the Mac-2 protein based on its lectin- and IgE-binding properties are discussed.

The membrane immunoglobulin heavy chain (micron) plays a feedback role during the pre-B stage of B lymphocyte differentiation. In pre-B cell lines, micron associates with two surrogate light chain proteins. The omega chain is disulfide linked to mu and was predicted to be the product of the lambda 5 gene. The iota chain is noncovalently associated with micron. We demonstrate that the omega protein is indeed the product of the lambda 5 gene and that mu, omega, and iota are coassociated in the same complex. Antibodies against the omega/lambda 5 protein demonstrate the existence of a subpopulation of "transitional" bone marrow B cells that express micron and omega on the cell surface. The majority of these cells also express surface kappa light chains, indicating that in B lymphoid ontogeny the lambda 5 gene is inactivated after the onset of kappa light chain expression.

The murine Mac-2 protein is a galactose- and IgE-binding lectin secreted by inflammatory macrophages. We describe here the cloning and characterization of a cDNA representing the human homolog of Mac-2 (hMac-2). The amino acid sequence derived from the hMac-2 cDNA indicates that the protein is evolutionarily highly conserved, with 85% of its amino acid residues being similar to those in the murine homolog. This conservation is especially marked in the carboxyl-terminal lectin domain. The amino-terminal half of the protein is less conserved but still contains the repetitive proline-glycine-rich motif seen in the mouse protein. hMac-2 synthesized in vitro is recognized by the M3/38 monoclonal antibody to Mac-2 and binds to the desialylated glycoprotein asialofetuin and to laminin, a major component of basement membranes. These findings are discussed in the context of the potential functions of hMac-2.

Proteins that bind to discrete domains of the Blk, Fyn, Lyn, and Btk protein tyrosine kinases were examined in pre-B cells that had not been subjected to any external stimulation, as well as in nonstimulated and antigen-receptor-ligated B cells. Proteins that bind to the Src homology 2 domains of Blk and Fyn were identified in B cells that had been activated with anti-IgM but were not identified in unstimulated B cells. A number of Blk and Fyn Src homology 2 domain-binding phosphoproteins were also observed in pre-B cells that had not been stimulated in vitro. The phosphoproteins seen in activated B cells potentially represent substrates that play a role in the pathway of antigen-receptor-mediated signaling. Distinct signaling pathways involving distinguishable kinase substrates may be relevant in pre-B-cell-receptor-mediated cell survival during ontogeny. These results indirectly support models that predict constitutive ligand-independent signaling by the pre-antigen receptor during lymphoid ontogeny.