Expression of Toll-like receptor 4 and 2 in horse lungs

Suri, Sarabjeet Singh; Janardhan, Kyathanahalli S.; Parbhakar, Om P.; Caldwell, Sarah; Appleyard, Greg D.; Singh, Baljit

doi:10.1051/vetres:2006017

Cited by 59 publications

(16 citation statements)

References 21 publications

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“…Our detection of TLR4 expression on AMs was in agreement with the results of Suri et al who reported TLR4 expression in healthy horse lungs (Suri et al, 2006). In the lungs there is a continuous challenge of AMs with airborne agents, which is not the case in the peritoneal cavity.…”

Section: Discussionsupporting

confidence: 93%

The equine alveolar macrophage: Functional and phenotypic comparisons with peritoneal macrophages

Karagianni¹,

Kapétanovic²,

McGorum³

et al. 2013

Veterinary Immunology and Immunopathology

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Alveolar macrophages (AMs) constitute the first line of defence in the lung of all species, playing a crucial role in the regulation of immune responses to inhaled pathogens. A detailed understanding of the function and phenotype of AMs is a necessary pre-requisite to both elucidating their role in preventing opportunistic bacterial colonisation of the lower respiratory tract and developing appropriate preventative strategies. The purpose of the study was to characterise this important innate immune cell at the tissue level by making functional and phenotypic comparisons with peritoneal macrophages (PMs). We hypothesised that the tissue of origin determines a unique phenotype of AMs, which may constitute an appropriate therapeutic target for certain equine respiratory diseases. Macrophages isolated from the lung and the peritoneal cavity of 9 horses were stimulated with various toll like receptor (TLR) ligands and the production of nitrite, tumour necrosis factor alpha (TNFα), interleukin (IL) 10 and indoleamine 2,3-dioxygenase (IDO) were measured by the Griess reaction and enzyme linked immunosorbent assay (ELISA) and/or quantitative polymerase chain reaction, respectively. Cells were also compared on the basis of phagocytic-capacity and the expression of several cell surface markers. AMs, but not PMs, demonstrated increased TNFα release following stimulation with LPS, polyinosinic polycytidylic acid (Poly IC) and heat-killed Salmonella typhinurium and increased TNFα and IDO mRNA expression when stimulated with LPS. AMs showed high expression of the specific macrophage markers cluster of differentiation (CD) 14, CD163 and TLR4, whereas PMs showed high expression of TLR4 only. AMs, but not PMs, demonstrated efficient phagocytic activity. Our results demonstrate that AMs are more active than PMs when stimulated with various pro-inflammatory ligands, thus supporting the importance of the local microenvironment in the activation status of the macrophage. This information provides a valuable knowledge base on which to improve our understanding of the role of macrophages and their microenvironment in equine innate immunity.

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Section: Discussionsupporting

confidence: 93%

The equine alveolar macrophage: Functional and phenotypic comparisons with peritoneal macrophages

Karagianni¹,

Kapétanovic²,

McGorum³

et al. 2013

Veterinary Immunology and Immunopathology

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“…It is well known that the Toll-like receptors (TLRs) are integral components of the innate immune system, recognizing the presence of microbial invaders via molecules such as LPS (6)(7)(8)(9). Recent studies indicate that TLRs share the capacity to bind the intracellular myeloid differentiation factor 88 (MyD88) (10,11).…”

mentioning

confidence: 99%

LPS-induced TNF-α factor (LITAF)-deficient mice express reduced LPS-induced cytokine: Evidence for LITAF-dependent LPS signaling pathways

Tang¹,

Metzger

Leeman

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

165

151

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Previously we identified a transcription factor, LPS-Induced TNF-α Factor (LITAF), mediating inflammatory cytokine expression in LPS-induced processes. To characterize the role of LITAF in vivo , we generated a macrophage-specific LITAF-deficient mouse (macLITAF −/− ). Our data demonstrate that in macrophages ( i ) several cytokines (such as TNF-α, IL-6, sTNF-RII, and CXCL16) are induced at lower levels in macLITAF −/− compared with LITAF +/+ control macrophages; ( ii ) macLITAF −/− mice are more resistant to LPS-induced lethality. To further identify LITAF signaling pathways, we tested mouse TLR-2 −/− , -4 −/− , and -9 −/− and WT peritoneal macrophages exposed to LPS. Using these cells, we now show that LITAF expression can be induced after challenge either with LPS from Porphyromonas gingivalis via agonism at TLR-2, or with LPS from Escherichia coli via agonism at TLR-4, both requiring functional MyD88. We also show that, in response to LPS, the MyD88-dependent LITAF pathway differs from the NF-κB pathway. Furthermore, using a kinase array, p38α was found to mediate LITAF phosphorylation and the inhibition of p38α with a p38-specific inhibitor (SB203580) blocked LITAF nuclear translocation and reduced LPS-induced TNF-α protein levels. Finally, macLITAF −/− macrophages rescued by LITAF cDNA transfection restored levels of TNF-α similar to those observed in WT cells. We conclude that LITAF is an important mediator of the LPS-induced inflammatory response that can be distinguished from NF-κB pathway and that p38α is the specific kinase involved in the pathway linking LPS/MyD88/LITAF to TNF.

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“…While the horse is more sensitive to LPS than other mammals that have been studied (including humans) [27], the innate immune response to LPS is very similar across species. This includes specific cell types and mediators involved in the inflammatory cascade following LPS challenge and is likely due to the fact that innate immunity is a highly conserved, evolutionarily old immune response [10].…”

Section: Discussionmentioning

confidence: 99%

“…The degree of LPS sensitivity seems to be species-specific and horses are one of the most sensitive animals in their response to LPS exposure, while rodents appear to be much more resistant [11, 27, 28]. Endotoxaemia plays a major role in many equine diseases, particularly in intestinal disorders like acute colitis and ischemic bowel diseases, which often present with colic as the principal clinical manifestation [29].…”

Section: Introductionmentioning

confidence: 99%

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

et al. 2017

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BackgroundLipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses.Results24 h-LPS challenge of equine immune cells resulted in substantial changes in the transcriptomic profile (1,265 differentially expressed genes) showing partial overlap with human data. One of the half-sib families showed a specific response different from the other two groups of horses. We also identified co-expressed gene modules that clearly differentiated 24 h-LPS- from non-stimulated samples. These modules consisted of 934 highly interconnected genes and included genes involved in the immune response (e.g. IL6, CCL22, CXCL6, CXCL2), however, none of the top ten hub genes of the modules have been annotated as responsive to LPS in gene ontology.ConclusionsUsing weighted gene co-expression network analysis we identified ten co-expressed gene modules significantly regulated by in vitro stimulation with LPS. Apart from 47 genes (5%) all other genes highly interconnected within the most up- and down-regulated modules were also significantly differentially expressed (FDR < 0.05). The LPS-regulated module hub genes have not yet been described as having a role in the immune response to LPS (e.g. VAT1 and TTC25).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3390-y) contains supplementary material, which is available to authorized users.

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Expression of Toll-like receptor 4 and 2 in horse lungs

Cited by 59 publications

References 21 publications

The equine alveolar macrophage: Functional and phenotypic comparisons with peritoneal macrophages

The equine alveolar macrophage: Functional and phenotypic comparisons with peritoneal macrophages

LPS-induced TNF-α factor (LITAF)-deficient mice express reduced LPS-induced cytokine: Evidence for LITAF-dependent LPS signaling pathways

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

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