Dataset Information

Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages.

ABSTRACT: While the presence of airway bacteria is known to be associated with improved immunity against influenza virus, the mechanism by which endogenous microbiota influence antiviral immunity remains unclear. Here we show that specific pathogen-free mice are more sensitive to influenza-mediated death than mice living in a natural environment. Priming with Toll-like receptor 2-ligand(+) Staphylococcus aureus, which commonly colonizes the upper respiratory mucosa, significantly attenuates influenza-mediated lung immune injury. Toll-like receptor 2 deficiency or alveolar macrophage depletion abolishes this protection. S. aureus priming recruits peripheral CCR2(+)CD11b(+) monocytes into the alveoli that polarize to M2 alveolar macrophages in an environment created by Toll-like receptor 2 signalling. M2 alveolar macrophages inhibit influenza-mediated lethal inflammation via anti-inflammatory cytokines and inhibitory ligands. Our results suggest a previously undescribed mechanism by which the airway microbiota may protect against influenza-mediated lethal inflammation.

SUBMITTER: Wang J

PROVIDER: S-EPMC3715851 | biostudies-other | 2013

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages.

Wang Jian J Li Fengqi F Sun Rui R Gao Xiang X Wei Haiming H Li Lan-Juan LJ Tian Zhigang Z

Nature communications 20130101

While the presence of airway bacteria is known to be associated with improved immunity against influenza virus, the mechanism by which endogenous microbiota influence antiviral immunity remains unclear. Here we show that specific pathogen-free mice are more sensitive to influenza-mediated death than mice living in a natural environment. Priming with Toll-like receptor 2-ligand(+) Staphylococcus aureus, which commonly colonizes the upper respiratory mucosa, significantly attenuates influenza-medi ...[more]

PMID: 23820884

Similar Datasets

Project description:Calreticulin (CALR) has anti-tumor effects by increasing dendritic cell maturation and tumor antigen presentation. However, whether CALR affects macrophages and modulates progression of acute respiratory distress syndrome/acute lung injury (ARDS/ALI) remains unknown. In this study, we discovered that CALR protein was highly expressed in the mice with LPS-induced ALI and CALR expression level was positively correlated to the severity of ALI. Commercial anti-CALR antibody (aCALR) can neutralize recombinant CALR (rCALR) and suppress the expression of TNF-alpha and IL-6 in the rCALR-treated macrophages. Blocking CALR activity by intraperitoneal (i.p.) administration of aCALR significantly suppressed ALI, accompanied with lower total cell counts, neutrophil and T cell infiltration in bronchoalveolar lavage (BAL) and lung tissues. The expression of CXCL15, IL-6, IL-1beta, TNF-alpha, and CALR were significantly reduced, in association with more polarization of Siglec F+CD206+M2 subtype macrophages in the aCALR-treated mice. Pre-depletion of circulating monocytes did not abolish the aCALR-mediated suppression of ALI. Further analysis in bone marrow-derived macrophages (BMDMs) showed that aCALR suppressed the expression of CD80, IL-6, IL-1beta, IL-18, NLRP3, and p-p38 MAPK; but enhanced the expression of CD206 and IL-10. In addition, we observed more expression and phosphorylation of STAT6 in the aCALR-treated BMDM. Lack of STAT6 resulted in comparable and slightly higher expression of CALR, TNF-alpha and IL-6 in the aCALR-treated STAT6-/- BMDMs than the untreated cells. Therefore, we conclude that CALR is a novel biomarker in the evaluation of ALI. Blocking CALR activity by aCALR effectively suppressed ALI independent of circulating monocytes. Siglec F+CD206+M2 subtype macrophages and p38 MAPK/STAT6 signaling pathway played important role in the immune regulation of aCALR. Blocking CALR activity is a promising therapeutic approach in the treatment of ARDS/ALI.

Project description:Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-? secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro-computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis-induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-? ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.

Dataset Information

Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages.

Publications

Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure