Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections with helminthic parasites occasionally induce pulmonary diseases with possible involvement of immunological mechanisms. In rats infected with the nematode Nippostrongylus brasiliensis, pulmonary granulomatous lesions develop and persist after the larvae have migrated through the lungs. To determine the pathogenesis of this lesion, we examined cytokine gene expression in the lungs using RT-PCR and in situ hybridization. Two weeks after infection, when fully developed lesions appeared, levels of IL-3 and of type2 cytokines IL-4, IL-5, IL-6 and IL-13 gene expression were markedly enhanced in whole lung homogenates. Those of IL-2 and IFN-gamma were also slightly increased 2 weeks postinfection. IL-12 mRNA level did not change after 2 weeks but was slightly increased after 4 weeks. Levels of IL-10 and proinflammatory cytokine TNF gene expression did not show significant changes, although a slight increase was observed in IL-1beta message after 2 weeks. In situ hybridization studies showed that lung granulomatous lesions were composed mainly of lymphoid cells expressing IL-3, IL-4 and IL-13 mRNA, but not IFN-gamma mRNA. IL-5 mRNA-expressing cells were fewer in number than these cells. RMCP II immunohistochemistry revealed that mast cells increased in number in the lung granulomas. From these results, it was concluded that the nematode infection-associated lung granuloma was a type 2 lesion.
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PMID:Type 2-biased expression of cytokine genes in lung granulomatous lesions induced by Nippostrongylus brasiliensis infection. 1130 32

Infection of different strains of laboratory mice with the agent of Lyme disease, Borrelia burgdorferi, results in arthritis, the severity of which has been correlated with the dominance of Th1 cytokines. In this study, we demonstrate that changes in B. burgdorferi-specific immunologic responses associated with pregnancy can alter the outcome of Lyme arthritis in mice. Whereas nonpregnant female C3H mice consistently developed severe Lyme arthritis, pregnant mice had a marked reduction in arthritis severity that was associated with a slight reduction in IFN-gamma and markedly increased levels of IL-4 production by B. burgdorferi-specific T cells. Similar reductions in arthritis severity and patterns of cytokine production were observed in nonpregnant, progesterone-implanted mice. Ab neutralization of IL-4 in progesterone-implanted mice resulted in severe arthritis. Our results are consistent with the known shift toward Th2 cytokine expression at the maternal-fetal interface, and are the first to show a pregnancy-related therapeutic effect in an infectious model.
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PMID:Gestational attenuation of Lyme arthritis is mediated by progesterone and IL-4. 1139 Apr 92

Two coxsackievirus B3 (CVB3) variants (H3 and H310A1) differ by a single amino acid mutation in the VP2 capsid protein. H3 induces severe myocarditis in BALB/c mice, but H310A1 is amyocarditic. Infection with H3, but not H310A1, preferentially activates Vgamma4 Vdelta4 cells, which are strongly positive for gamma interferon (IFN-gamma), whereas Vgamma1 Vdelta4 cells are increased in both H3 and H310A1 virus-infected animals. Depletion of Vgamma1(+) cells using monoclonal anti-Vgamma1 antibody enhanced myocarditis and CD4(+)-, IFN-gamma(+)-cell responses in both H3- and H310A1-infected mice yet decreased the CD4(+)-, IL-4(+)-cell response. Depleting Vgamma4(+) cells suppressed myocarditis and reduced CD4(+) IFN-gamma(+) cells but increased CD4(+) IL-4(+) T cells. The role of cytokine production by Vgamma1(+) and Vgamma4(+) T cells was investigated by adoptively transferring these cells isolated from H3-infected BALB/c Stat4 knockout (Stat4ko) (defective in IFN-gamma expression) or BALB/c Stat6ko (defective in IL-4 expression) mice into H3 virus-infected wild-type BALB/c recipients. Vgamma4 and Vgamma1(+) T cells from Stat4ko mice expressed IL-4 but no or minimal IFN-gamma, whereas these cell populations derived from Stat6ko mice expressed IFN-gamma but no IL-4. Stat4ko Vgamma1(+) cells (IL-4(+)) suppress myocarditis. Stat6ko Vgamma1(+) cells (IFN-gamma(+)) were not inhibitory. Stat6ko Vgamma4(+) cells (IFN-gamma(+)) significantly enhanced myocarditis. Stat4ko Vgamma4(+) cells (IL-4(+)) neither inhibited nor enhanced disease. These results show that distinct gammadelta-T-cell subsets control myocarditis susceptibility and bias the CD4(+)-Th-cell response. The cytokines produced by the Vgamma subpopulation have a significant influence on the CD4(+)-Th-cell phenotype.
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PMID:Cytokine production by Vgamma(+)-T-cell subsets is an important factor determining CD4(+)-Th-cell phenotype and susceptibility of BALB/c mice to coxsackievirus B3-induced myocarditis. 1139 May 87

Onchocerciasis is a debilitating parasitic infection caused by the filarial nematode Onchocerca volvulus. Infections are chronic, and persistence of the parasites for several years argues for highly adapted mechanisms of immune evasion. Due to the restricted host repertoire of O. volvulus, we have used the cattle parasite Onchocerca ochengi to investigate the nature of immunomodulation underpinning these long-term infections. Cattle were infected with a single inoculation of 350 infective-stage larvae under laboratory conditions (n = 6). Intradermal nodules containing immature adult worms were detected from 110 days postinfection, and microfilariae in skin were detected from day 280 postinfection. Parasite-specific responses during early infection were nonpolarized with respect to the major Th cytokines (interleukin-4 [IL-4], IL-2, and gamma interferon [IFN-gamma]) produced by antigen-stimulated peripheral blood mononuclear cells (PBMC) or serum antibody isotypes. Antigen-induced proliferation of PBMC peaked shortly after exposure and remained high during the prepatent infection. As the parasites matured and animals developed patent infections, there was a profound down-regulation of lymphoproliferation, accompanied by sharp falls in the expression of both IL-4 and IFN-gamma and a gradual decline in IL-2. Levels of immunoglobulin G2 (IgG2) fell, while those of IgG1 remained high. We conclude that neither a classical Th2 response nor a simple Th1-to-Th2 switch is sufficient to explain the immunomodulation associated with patent Onchocerca infections. Instead, there is an initial Th0 response, which matures into a response with some, but not all of the features of a Th2 response. The natural host-parasite relationship of O. ochengi in cattle may be useful as both a descriptive and predictive tool to test more refined models of immunomodulation in onchocerciasis.
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PMID:Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis. 1140 68

We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with infectious agents, recapitulated features of XLP. Infection of SAP- mice with lymphocyte choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell activation and IFN-gamma production, as well as a reduction of Ig-secreting cells. Anti-CD3-stimulated splenocytes from uninfected SAP- mice produced increased IFN-gamma and decreased IL-4, findings supported by decreased serum IgE levels in vivo. The Th1 skewing of these animals suggests that cytokine misregulation may contribute to phenotypes associated with mutation of SH2D1A/SAP.
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PMID:Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. 1140 75

The progressive disease following Leishmania amazonensis infection in mice requires functional CD4(+) T cells, which are primed to a disease-promoting phenotype during the infection. To understand how these pathogenic T cells are generated and the role of dendritic cells (DCs) in this process, we use DCs of susceptible BALB/c and resistant C3H/HeJ mice to examine parasite-DC interactions in vitro as well as the effector phenotype of T cells primed by parasite-exposed DCs in vivo. Our results demonstrate that amastigotes and metacyclics efficiently enter and activate DCs of both genetic backgrounds. Infection with amastigotes fails to induce CD40-dependent IL-12 production, but rather potentiates IL-4 production in BALB/c DCs. Upon transfer into syngeneic recipients, amastigote-exposed BALB/c DCs prime parasite-specific Th cells to produce significantly higher levels of IL-4 and IL-10 than their C3H/HeJ counterparts. Transfer studies with IL-4(-/-) DCs indicate that this enhanced Th2 priming seen in BALB/c mice is partially due to the IL-4 production by amastigote-carrying DCs. These results suggest that L. amazonensis amastigotes may condition DCs of a susceptible host to a state that favors activation of pathogenic CD4(+) T cells, and thereby provide a new perspective on the pathogenesis of cutaneous leishmaniasis and protozoan parasite-host interactions in general.
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PMID:Leishmania amazonensis-dendritic cell interactions in vitro and the priming of parasite-specific CD4(+) T cells in vivo. 1159 81

Cytokines are key communication molecules between host cells in the defense against the enteric pathogen, Salmonella. Infection with Salmonella induces expression of multiple chemokines and proinflammatory cytokines in cultured intestinal epithelial cells and macrophages. In animal models, protective roles have been shown for IL-1alpha, TNFalpha, IFN-gamma, IL-12, IL-18 and IL-15, whereas IL-4 and IL-10 inhibit host defenses against Salmonella.
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PMID:Cytokines in host defense against Salmonella. 1175 7

Infection with Leishmania major in BALB/c mice is accompanied by the development of a nonprotective Th2-type response. It has previously been shown that disease progression, and the activation of a Th2-type response, can occur in the absence of CD28 costimulation following the inoculation of high numbers of L. major promastigotes. In this study, we show that in the absence of CD28-B7 interactions, BALB/c mice can spontaneously resolve their infections following the inoculation of low numbers of parasites. BALB/c CD28+/+ and CD28-/-mice were inoculated with 250, 500, and 750 metacyclic parasites. The CD28-/- mice controlled their lesions, whereas the wild-type (WT) mice developed progressive nonhealing infections. Resistance to infection was associated with reduced numbers of parasites in the CD28-/- mice compared with the WT mice. Infection of the CD28-/- mice resulted in the activation of a Th1-type response as evidenced by increased levels of mRNA for IFN-gamma and reduced levels of message for IL-4 and IL-10 in draining lymph nodes compared with those in WT mice. Healing of infected CD28-/- mice could also be ablated with anti-CD4 Ab treatment or treatment with anti-IFN-gamma Ab. In addition, healed CD28-/- mice were resistant to a challenge infection with L. major. These results suggest that CD28 costimulation influences the in vivo activation of a Th2-type response in a manner that is dependent on the size of the parasite inoculum.
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PMID:CD28 costimulation and parasite dose combine to influence the susceptibility of BALB/c mice to infection with Leishmania major. 1180 69

Infection with Mycobacterium tuberculosis induces Abs against a vast array of mycobacterial lipids and glycolipids. One of the most prominent lipid Ags recognized is cardiolipin (CL). The kinetics of the generation of anti-CL Abs during infection reveals that IgM titers to CL increase over time. Interestingly, at day 30 postinfection CL-specific IgG1 appears, an isotype usually dependent on T cell help. Using an immunization schedule with CL/anti-CL Ab complexes, which induces antiphospholipid syndrome in mice, we show that the generation of IgG1 to CL requires IL-4 and that optimal production is T cell dependent. IgG1 production to CL was impaired in nude (nu/nu) mice devoid in conventional T cells, but was not affected in mice deficient for either alphabeta TCR(+), gammadelta TCR(+), CD4(+), CD8(+), or NK1.1(+) T cells. We conclude that IgG1 production to CL depends on T cell help and IL-4, which can be provided by different T cell populations. This is the first report that IL-4 is indispensable for the induction of IgG1 Abs to lipid Ags.
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PMID:IL-4 and T cells are required for the generation of IgG1 isotype antibodies against cardiolipin. 1188 34

Infection of mice with Schistosoma mansoni delays the resolution of cutaneous lesions and parasitaemia during Leishmania major infection. In contrast, L. major infection does not appear to alter the course of schistosomiasis. Analysis of the cytokine responses in the draining lymph nodes (LN) indicates that, while L. major infection had no effect on schistosome-specific interleukin (IL)-4 production by mesenteric LN (MLN) cells, coinfection with S. mansoni resulted in decreased leishmania-induced interferon (IFN)-gamma, tumour necrosis factor-alpha and nitric oxide production by popliteal LN (PLN) cells 4 weeks after L. major infection. In addition, PLN cells produced higher levels of IL-4 4 weeks after L. major infection in coinfected mice. Finally, IFN-gamma-stimulated macrophages isolated from S. mansoni-infected mice were impaired in their ability to kill L. major after in vitro infection. These results suggest that pre-existence of a strong Th2 response-dominated infection can alter the responses to Th1-inducing pathogens at peripheral sites and impair Th1-mediated effector functions.
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PMID:Schistosomiasis delays lesion resolution during Leishmania major infection by impairing parasite killing by macrophages. 1577 78


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