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Cell Pathways (cell + pathway)
Selected AbstractsExperimental African trypanosomiasis: lack of effective CD1d-restricted antigen presentationPARASITE IMMUNOLOGY, Issue 12 2006M. Q. SHI SUMMARY BALB/c mice are highly susceptible to African trypanosomiasis, whereas C57BL/6 mice are relatively resistant. Other investigators have reported that the synthesis of IgG antibodies to purified membrane form of variant surface glycoprotein (mfVSG) of Trypanosoma brucei is CD1 restricted. In this study, we examine the role of the CD1d/NKT cell pathway in susceptibility and resistance of mice to infection by African trypanosomes. Administration of anti-CD1d antibodies to Trypanosoma congolense -infected BALB/c mice neither affects the parasitemia nor the survival time. Correspondingly, CD1d,/, and CD1d+/+ BALB/c mice infected with T. congolense or T. brucei show no differences in either parasitaemia or survival time. The course of disease in relative resistant C57BL/6 mice infected with T. congolense is also not affected by the absence of CD1d. Parasitaemia, survival time, and plasma levels of IgG2a and IgG3 parasite-specific antibodies in infected CD1d,/, C57BL/6 are not different from those of infected CD1d+/+ C57BL/6 mice. We conclude that CD1d-restricted immune responses do not play an important role in susceptibility/resistance of mice infected with virulent African trypanosomes. We speculate that virulent trypanosomes have an evasion mechanism that prevents the induction of a parasite-specific, CD1d-restricted immune response by the host. [source] Activity alters muscle reinnervation and terminal sprouting by reducing the number of schwann cell pathways that grow to link synaptic sitesDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2003Flora M. Love Abstract In partially denervated rodent muscle, terminal Schwann cells (TSCs) located at denervated end plates grow processes, some of which contact neighboring innervated end plates. Those processes that contact neighboring synapses (termed "bridges") appear to initiate nerve terminal sprouting and to guide the growth of the sprouts so that they reach and reinnervate denervated end plates. Studies conducted prior to knowledge of this potential involvement of Schwann cells showed that direct muscle stimulation inhibits terminal sprouting following partial denervation (Brown and Holland, 1979). We have investigated the possibility this inhibition results from an alteration in the growth of TSC processes. We find that stimulation of partially denervated rat soleus muscle does not alter the length or number of TSC processes but does reduce the number of TSC bridges. Stimulation also reduces the number of TSC bridges that form between end plates during reinnervation of a completely denervated muscle. The nerve processes ("escaped fibers") that normally grow onto TSC processes during reinnervation are also reduced in length. Therefore, stimulation alters at least two responses to denervation in muscles: (1) the ability of TSC processes to form or maintain bridges with innervated synaptic sites, and (2) the growth of axons along processes extended by TSCs. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 566,576, 2003 [source] Addressing the effects of Salmonella internalization in host cell signaling on a reverse-phase protein arrayPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 14 2009Cristina Molero Abstract Through acute enteric infection, Salmonella invades host enterocytes and reproduces intracellularly into specialized vacuolae. This involves changes in host cell signaling elicited by bacterial proteins delivered via type III secretion systems (TTSS). One of the two TTSSs of Salmonella enterica serovar Typhimurium encoded by the Salmonella pathogenicity island-1, triggers bacterial internalization. Among the effector proteins translocated by this TTSS, the GTPase modulator SopE/E2 and the phosphoinositide phosphatase SigD are known to play key roles in these processes. To better understand their contribution to re-programming host cell pathways, we used ZeptoMARK reverse-phase protein array technology, which allows printing 32-sample lysate arrays that can be analyzed with phospho-specific antibodies to evaluate the phosphorylation of signaling proteins. Lysates were obtained at different times after infection of HeLa cells with WT, TTSS-deficient, sopE/E2 and sigD single and double deletants, as well as different sigD Salmonella mutants. Our analysis detected activation of p38, JNK and ERK mitogen-activated protein kinases, mainly dependent on SopE/E2, as well as SigD-dependent phosphorylation of PKB/Akt and its targets GSK-3, and FKHR/FoxO. This is the first time that reverse-phase protein array technology is used in the cellular microbiology field, demonstrating its value to screen for host signaling events through bacterial infection. [source] Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: Evidence of possible gene,gene interaction and alterations in Th1/Th2 cytokinesARTHRITIS & RHEUMATISM, Issue 12 2009Pravitt Gourh Objective Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Dysregulation of the immune system, including the Th1/Th2 cytokine balance, is central to the pathogenesis of SSc. This study was undertaken to investigate the hypothesis that single-nucleotide polymorphisms (SNPs) in TBX21 and STAT4, both of which are critical transcription factors that regulate the Th1/Th2 balance, are associated with SSc susceptibility. Methods We tested SNPs in TBX21 and STAT4 for association with SSc in 2 independent cohorts, the SSc Registry cohort (880 SSc cases and 507 controls) and the University of Texas SSc cohort (522 cases and 531 controls). Additional white control genotypes were obtained from public repositories. We also investigated for gene,gene interactions. Plasma cytokines and whole blood gene expression profiles were examined to determine functional effects of these SNPs. Results Multiple SNPs in TBX21 and STAT4 were found to be associated with SSc. In a combined analysis of 902 SSc patients and 4,745 controls, TT genotyping of the TBX21 rs11650354 variant revealed a recessive pattern for disease susceptibility (Pcorr = 1.4 × 10,15, odds ratio 3.37, 95% confidence interval 2.4,4.6). In an analysis of 1,039 SSc patients and 3,322 controls, the A allele of the STAT4 variant rs11889341 was associated with increased SSc susceptibility in a dominant pattern (Pcorr = 2.4 × 10,5, odds ratio 1.29, 95% confidence interval 1.2,1.5). Furthermore, we identified gene,gene interaction among the TBX21 and STAT4 variants, such that the STAT4 genotype increased the risk of SSc only in the TBX21 CC genotype group. SSc patients carrying the TBX21 CC genotype had higher interleukin-6 (IL-6) and tumor necrosis factor , levels, and those with the TT genotype had elevated IL-2, IL-5, IL-4, and IL-13 (Th2) levels, compared with controls. Whole blood expression profiles revealed dysregulation of type I interferon pathways in the CC group and T cell pathways in the TT group of the TBX21 SNP. Conclusion The present results, from studies of 2 independent cohorts, indicate that SNPs in TBX21 and STAT4 contribute uniquely and interactively to SSc susceptibility, leading to altered cytokine balance and immune dysregulation. [source] Show me the substrates: modulation of host cell function by type IV secretion systemsCELLULAR MICROBIOLOGY, Issue 6 2003Hiroki Nagai Summary Evidence for the involvement of type IV protein secretion systems in bacterial virulence is accumulating. Many of the substrate proteins secreted by type IV systems either hijack or interfere with specific host cell pathways. These substrates can be injected directly into host cells via the type IV apparatus or are secreted by the type IV machinery in a state that allows them to gain access to cellular targets without the further assistance of the type IV system. Arguably, the protein substrates of most type IV secretion systems remain undiscovered. Here, we review the activities of known type IV substrates and discuss the putative roles of unidentified substrates. [source] | |||||||||||||