Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The differentiation of monocytes into dendritic cells (DC) is a key mechanism by which the innate immune system instructs the adaptive T cell response. In this study, we investigated whether leukocyte Ig-like receptor A2 (LILRA2) regulates DC differentiation by using leprosy as a model. LILRA2 protein expression was increased in the lesions of the progressive, lepromatous form vs the self-limited, tuberculoid form of leprosy. Double immunolabeling revealed LILRA2 expression on CD14+, CD68+ monocytes/macrophages. Activation of LILRA2 on peripheral blood monocytes impaired GM-CSF induced differentiation into immature DC, as evidenced by reduced expression of DC markers (MHC class II, CD1b, CD40, and CD206), but not macrophage markers (CD209 and CD14). Furthermore, LILRA2 activation abrogated Ag presentation to both CD1b- and MHC class II-restricted, Mycobacterium leprae-reactive T cells derived from leprosy patients, while cytokine profiles of LILRA2-activated monocytes demonstrated an increase in TNF-alpha, IL-6, IL-8, IL-12, and IL-10, but little effect on TGF-beta. Therefore, LILRA2 activation, by altering GM-CSF-induced monocyte differentiation into immature DC, provides a mechanism for down-regulating the ability of the innate immune system to activate the adaptive T cell response while promoting an inflammatory response.
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PMID:LILRA2 activation inhibits dendritic cell differentiation and antigen presentation to T cells. 1805 55

Interleukin (IL)-17 is a proinflammatory cytokine which induces differentiation and migration of neutrophils through induction of cytokines and chemokines including granulocyte-colony stimulating factor and CXCL8/IL-8. IL-17-producing CD4(+) T cells (Th17) have pivotal role in pathogenesis of autoimmune diseases. IL-17 is also involved in protective immunity against various infections. IL-17 has important role in induction of neutrophil-mediated protective immune response against extracellular bacterial or fungal pathogens such as Klebsiella pneumoniae and Candida albicans. Importance of IL-17 in protection against intracellular pathogens including Mycobacterium has also been reported. Interestingly, not only CD4(+) T cells but atypical CD4(-)CD8(-) T cells expressing T cell receptor (TCR) gammadelta produce IL-17, and IL-17 producing cells participate in both innate and acquired immune response to infections. Furthermore, neutrophil induction may not be the only mechanism of IL-17-mediated protective immunity. IL-17 seems to participate in host defense through regulation of cell-mediated immunity or induction of antimicrobial peptides such as beta-defensins. In this review, we summarize recent progress on the role of IL-17 in immune response against infections, and discuss possible application of IL-17 in prevention and treatment of infectious diseases.
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PMID:Interleukin-17 as an effector molecule of innate and acquired immunity against infections. 1809 32

Non-pathogenic mycobacteria, like Mycobacterium gordonae, are rarely associated to disease. The analysis of the mechanisms which are successful against them in the human host may provide useful information to understand why they fail against the pathogenic M. tuberculosis. We have developed an infection model to test the ability of human phagocytes to kill two strains of M. gordonae, HL184G and an attenuated variety, HL184Gat. As controls we included a strain of M. tuberculosis (HL186T) and another one of L. pneumophila (ATCC13151). We observed that human phagocytes lack the intrinsic ability to eliminate either M. gordonae or M. tuberculosis, but they can kill the attenuated strain. We found a relationship between pathogenicity and the pattern of cytokine production. Thus, both the pathogenic M. tuberculosis and Legionella pneumophila, but not the non-pathogenic M. gordonae, induced the production of significantly different levels of IL-1beta, IL-6 and TNF-alpha in monocytes and IL-8 in neutrophils. Although both monocytes and neutrophils killed HL184Gat, but not HL184G, the patterns of cytokine production induced by either strain were identical. Addition of INF-gamma and/or TNF-alpha did not enhance the antimycobacterial activity of phagocytes.
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PMID:Human phagocytes lack the ability to kill Mycobacterium gordonae, a non-pathogenic mycobacteria. 1816 Jan 7

The predominant extrapulmonary form of tuberculosis, which develops in 10% of diseased individuals, is pleurisy. The immune response mounted against Mycobacterium tuberculosis in the pleural cavity is one that is sufficient for clearing the organism without therapeutic intervention. Thus, examining the role of immune constituents in this context will provide understanding of the vital role they play in controlling tuberculosis. In this study, experimental tuberculous pleurisy was induced in guinea pigs, and anti-TGF-beta was administered intrapleurally to the guinea pigs daily throughout the study (8 days). Neutralizing TGF-beta resulted in a significant reduction in the percentage of lymphocytes and CD8+ cells present in the pleural exudate, decreased proliferative responses of pleural cells to ConA and PPD, and decreased mRNA expression of IFN-gamma and CCL5 in pleural effusion cells. Conversely, the percentage of neutrophils was significantly increased in anti-TGF-beta-treated guinea pigs, along with upregulated mRNA expression of CXCL8. The percentage of macrophages in the pleural exudate, TNF-alpha and IL-12p40 mRNA expression, and the histopathological response were not significantly altered. While TGF-beta is generally thought of as an immunosuppressive cytokine, the results of this study demonstrate its importance in promoting an inflammatory response, and highlight its bipolar nature.
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PMID:Altered inflammatory responses following transforming growth factor-beta neutralization in experimental guinea pig tuberculous pleurisy. 1855 47

Comparative genomics has identified several regions of differences (RDs) between the infectious Mycobacterium tuberculosis and the vaccine strains of Mycobacterium bovis BCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-gamma), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 6 [IL-6], IL-8, and IL-1beta), Th1 cytokines (IFN-gamma, IL-2, and TNF-beta), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-gamma and IL-10, with high IFN-gamma/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-gamma/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest that M. tuberculosis RDs can be divided into two major groups--one group that activates PBMC to preferentially secrete IFN-gamma and another group that activates preferential secretion of IL-10--and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.
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PMID:Characterization of human cellular immune responses to novel Mycobacterium tuberculosis antigens encoded by genomic regions absent in Mycobacterium bovis BCG. 1857 97

Dendritic cells (DCs) play a key role in the host immune response to infections. Mycobacterium tuberculosis (MTB) can inhibit the maturation of DCs and impair their ability to stimulate T cell proliferation. Here, we assessed in vitro migratory behavior of human monocyte-derived DCs (MoDC) when infected with various MTB strains (H37Rv and prevalent clinical strains S7 and S10 from South India). The migration of Rv and S7 infected MoDC towards secondary lymphoid chemokine (CCL21) was 50% lower after 1 day of infection compared to LPS stimulation. This reduced cell migration may be due to a block in the chemokine receptor switch from CCR5 to CCR7 expression on MoDC. Only clinical strain S10 infected MoDC showed an up-regulation of CCR7 and down-regulation of CCR5 expression, similar to LPS stimulated MoDC. While Rv and S7 infected MoDC did not display any alteration in expression of these receptors. Similarly, Rv and S7 infected MoDC did not induce IL-8, IP-10 and MCP-1 chemokine production. This reduction in chemokine levels was reflected in the reduced chemoattraction of CD4(+) T cells also. These findings suggest that there is variation in the stimulation of MoDC with different clinical strains of MTB and this variation may be dependent upon the virulence of the strain.
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PMID:Differential migration of human monocyte-derived dendritic cells after infection with prevalent clinical strains of Mycobacterium tuberculosis. 1865 4

Tuberculosis (TB) pleurisy is accepted to be the best model for evaluating the local protective cellular immune response to Mycobacterium tuberculosis (MTB) since it can be spontaneously self-cured. Therefore, we aimed to evaluate the involvement of cytokines and the soluble apoptosis-modulating factors sFas and sFasL in local protective cellular immunity to MTB. Pleural fluid samples were collected from 35 patients with TB pleurisy, 39 patients with malignant pleurisy, and 14 patients with non-TB nonmalignant (n-TB n-M) pleurisy and were evaluated for the levels of several cytokines, soluble Fas (sFas), and sFas ligand (sFasL) by using ELISA. The levels of IFN-gamma, IL-12p40, IL-18, IL-8, and sFasL in TB pleurisy were significantly higher in comparison to those in the malignant pleurisy and n-TB n-M pleurisy groups. In addition, pleural sFasL levels were increased and positively correlated with IFN-gamma and IL-18 levels in TB patients. In conclusion, this study demonstrates that Th1-type-specific cellular immunity is responsible for protective immunity in TB and suggests that Fas-mediated apoptosis may be at least a part of protective immunity to tuberculosis and could be regulated by type 1 T-cell response. IFN-gamma and sFasL levels can be used as diagnostic markers for differing TB pleurisy from other pleurisies.
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PMID:Increased pleural soluble fas ligand (sFasL) levels in tuberculosis pleurisy and its relation with T-helper type 1 cytokines. 1866 30

Mycobacterium avium subspecies paratuberculosis (MAP) is a facultative intracellular organism that resides in host macrophages. MAP causes a fatal wasting syndrome in ruminants, typified by granulomatous enteritis in the small intestine. MAP has also been suspected as a causative or exacerbating factor in some cases of human Crohn's disease. In MAP infections, a cytotoxic and proinflammatory Th1-like response is essential to control disease. While such a response may initially develop, this typically gives way to a Th2-like response later in infection. Interaction between CD40 receptors on macrophages and CD154 (CD40L) on activated T cells is crucial for maintaining a Th1 response and activation of macrophages. In this report, we investigated the hypothesis that CD40 signalling is impaired in MAP-infected macrophages. Uninfected bovine monocyte-derived macrophages (MDM) responded to CD40L by up-regulating expression of genes encoding IL-6, TNFalpha, IL-8, iNOS, IL-10, and IL-12p40. In contrast, MDM cells infected with MAP failed to up-regulate expression of iNOS and IL-12p40 genes in response to CD40L. CD40L stimulation caused a transient activation of the mitogen-activated protein kinase (MAPK) family member extracellular signal-regulated kinases (ERK) 1/2, stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) and p38 in MDM cells. In uninfected cells, inhibition of MAPK revealed that CD40L-mediated increase in IL-6 gene expression was dependent on activation of ERK1/2, while increases in IL-12p40, iNOS, and IL-10 gene expression were dependent on activation of p38. Because early activation of p38 was unimpaired in MAP-infected macrophages, we propose that MAP interferes with gene expression of iNOS and IL-12p40 genes downstream of p38.
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PMID:Mycobacterium avium subspecies paratuberculosis suppresses expression of IL-12p40 and iNOS genes induced by signalling through CD40 in bovine monocyte-derived macrophages. 1902 5

Mycobacterium ulcerans (MU), an environmental pathogen, causes Buruli ulcer, a severe skin disease. We hypothesized that epidermal keratinocytes might not be a simple barrier, but play a role during MU infection through pattern-recognition receptors expressed in keratinocytes. We found that keratinocyte Toll-like receptors (TLRs) 2 and 4 and Dectin-1 actively participate in the innate immune response to MU, which includes the internalization of bacteria, the production of reactive oxygen species (ROS), and the expression of chemokines and LL-37. Human keratinocytes constitutively expressed TLRs 2 and 4 and induced Dectin-1 in response to MU. Exposing keratinocytes to MU resulted in rapid ROS production, which in turn contributed to the mRNA and protein expression of LL-37. In addition, TLR2, Dectin-1 and, to an extent, TLR4 are essential for the MU-mediated expression of CXCL8, CCL2 and LL-37 in keratinocytes. Furthermore, confocal analysis showed that the Dectin-1 is necessary for keratinocytes to internalize bacilli. Importantly, blockade of ROS and LL-37 significantly increased the intracellular MU growth in keratinocytes, suggesting an important role of these mediators for cutaneous innate immune responses. Our results demonstrate that TLR2, TLR4 and Dectin-1 actively sense, internalize and respond in an innate way to MU in human epidermal keratinocytes.
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PMID:Innate immune responses to Mycobacterium ulcerans via toll-like receptors and dectin-1 in human keratinocytes. 1913 18

Chemokines and their receptors orchestrate leukocyte recruitment and confer immunity during Mycobacterium tuberculosis infection. The immunoregulatory and cytotoxic activities of natural killer (NK) cells are essential at the site of infection during tuberculous pleurisy. The frequency, subtypes, and expression of phenotype markers and chemokine receptors on NK cells were assessed by flow cytometry in tuberculous (TB) and nontuberculous (NTB) pleural fluid (PF). Chemotaxis was also shown in response to chemokines. A significant decrease in CD56(dim) with no change in CD56(bright) NK cells was observed, while a significant increase in activation markers and Toll-like receptors (TLRs) was observed on TB-PF CD56(bright) NK cells. Significantly increased expression of chemokine receptors CCR1, CCR2 and CCR7 on CD56(bright) and CCR5 on CD56(dim) NK cells was observed in the TB group. Transmigration of TB-PF NK cells was significantly high in response to IL-8, IP-10, MCP-1 and SLC. Transmigrated TB-NK cells showed a significant increase in CXCR2, CCR2 and CCR7 expression. The study suggests that CD56(bright) NK cells may recognize M. tuberculosis directly using TLRs, HLA-DR and express CD69 as an early activation marker. In addition, CC chemokines induce activation signals in chemokine receptors mediating differential NK cell migration to the site. Thus, NK cells act as first direct sensors and effectors in mycobacterial infection.
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PMID:Differential upregulation of chemokine receptors on CD56 NK cells and their transmigration to the site of infection in tuberculous pleurisy. 1915 32


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