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Granulomatous Response (granulomatous + response)

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Medical Sciences	100%

Selected Abstracts

TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008
Amrita D. Joshi
Abstract We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3+/+) and TLR3 gene-deficient (TLR3,/,) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni -sensitized TLR3+/+ mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3,/, mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3+/+ mice. Macrophages from TLR3,/, mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4+CD25+ T cells were present in the lungs of TLR3,/, mice compared with TLR3+/+ mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3,/, mice released significantly higher levels of IL-17 levels relative to TLR3+/+ cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology. [source]

TLR9 activation is a key event for the maintenance of a mycobacterial antigen-elicited pulmonary granulomatous response

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007
Toshihiro Ito
Abstract Type 1 (Th1) granulomas can be studied in mice sensitized with mycobacterium antigens followed by challenge of agarose beads covalently coupled to purified protein derivative. TLR9 is known to play a role in the regulation of Th1 responses; thus, we investigated the role of TLR9 in granuloma formation during challenge with mycobacterium antigens and demonstrated that mice deficient in TLR9 had increased granuloma formation, but a dramatically altered cytokine phenotype. Th1 cytokine levels of IFN-, and IL-12 in the lungs were decreased in TLR9,/, mice when compared to wild-type mice. In contrast, Th2 cytokine levels of IL-4, IL-5, and IL-13 were increased in TLR9,/, mice. The migration of CD4+ T cells in the granuloma was impaired, while the number of F4/80+ macrophages was increased in TLR9,/, mice. Macrophages in the lungs of the TLR9-deficient animals with developing granulomas expressed significantly lower levels of the classically activated macrophage marker, nitric oxide synthase, but higher levels of the alternatively activated macrophage markers such as ,found in inflammatory zone-1, antigen and Arginase-1. These results suggest that TLR9 plays an important role in maintaining the appropriate phenotype in a Th1 granulomatous response. [source]

Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2002
D. A. LAMMAS
Summary Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. These experiments of nature demonstrate that IL-12-dependent IFN, production is critical for granuloma formation and therefore host immunity against such pathogens. The essential role of granuloma formation for protective immunity to these organisms is emphasized by the differing granuloma forming capabilities and resultant clinical sequelae observed in these patients which seems to reflect their ability to produce or respond to IFN, (Fig. 9). At one pole of this spectrum, represented by the complete IFN,R1/2 deficient patients, there is a complete absence of mature granuloma formation, whereas with the less severe mutations (i.e. partial IFN,R1/2, complete IL-12p40 and complete IL-12R,1 deficiency), granuloma formation is very heterogenous with wide variations in composition being observed. This suggests that in the latter individuals, who produce partial but suboptimal IFN, responses, other influences, including pathogen virulence and host genotype may also affect the type and scale of the cellular response elicited. Figure 9. ,Spectrum of genetic susceptibility to intracellular bacteria. At one pole of this spectrum complete IFN,R deficiencies are found; at the other pole are healthy resistant individuals. Partial IFN,R1 deficiencies, and complete IL-12R,1 and IL-12p40 deficiencies can be positioned in between, albeit closer to the former end of the spectrum, with clinical outcome also depending on pathogen virulence and host compensatory immune mechanism(s). Abbreviations: IFN,R , interferon gamma receptor, IL-12R,1 , interleukin 12 receptor-1 (modified from Ottenhoff et al. (1998)). [source]

Chemokine responses in schistosomal antigen-elicited granuloma formation,

PARASITE IMMUNOLOGY, Issue 6 2002
Bo-Chin Chiu
Summary Host immune systems have evolved specialized responses to multicellular parasites. This is well represented by the type 2 granulomatous response to Schistosoma mansoni egg antigens, which is an eosinophil-rich inflammatory response mediated by Th2-associated cytokines. Using Ag-bead models of pulmonary granuloma formation in mice, we defined characteristic chemokine (CK) profiles in the granulomatous lungs. Our findings point to a role for C-C chemokine receptor-2 (CCR2) and CCR3 agonists such as monocyte chemotactic proteins (MCPs) 1/CCL2, 3/CCL7 and 5/CCL12 as important participants that are subject to regulation by Th2 cytokines interleukin (IL)-4 and IL-13. CCR4 and CCR8 agonists are also likely contributors. Analysis of CK receptor knockout mice revealed that CCR2 ligands (e.g. MCP-1 and 5) promoted early phase granuloma macrophage accumulation, whereas anti-MCP-3 (CCL7) antibody treatment abrogated eosinophil recruitment. CCR8 knockout mice also demonstrated impaired eosinophil recruitment but this appeared to be related to impaired Th2 cell function. Transcript analysis of CD4+ T cells generated during schistosome granuloma formation failed to show biased CCR8 expression but, having a more limited receptor repertoire, these cells were likely more dependent on CCR8 ligands. Together, these studies indicate an intricate involvement of chemokines in various stages and aspects of schistosomal egg Ag-elicited granuloma formation. [source]

Pseudallescheria boydii or Aspergillus fumigatus in a lady with an unresolving lung infiltrate, and a literature review

RESPIROLOGY, Issue 3 2008
Sin-Man LAM
Abstract: A 53-year-old lady with blood-stained sputum and pleuritic pain had a lingular opacity on CXR which failed to resolve. A bronchial aspirate and transbronchial biopsy revealed features of bronchocentric granulomatosis with dichotomous branching hyphae suggestive of Aspergillus infection. However, subsequent fungal culture grew Pseudallescheria boydii. This case demonstrates the similarity of clinical and histological features caused by these two fungi. This appears to be the first reported case of pulmonary pseudallescheria with a bronchocentric granulomatous response. [source]