CD14-Mac-1 interactions in<i>Bacillus anthracis</i>spore internalization by macrophages

Oliva, Claudia R.; Turnbough, Charles L.; Kearney, John F.

doi:10.1073/pnas.0902392106

Cited by 78 publications

(83 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We show here that CD14-neutralizing antibody attenuates LPSinduced signal transduction in MLE12 cells. Recent studies demonstrated that, in addition to LBP, CD14 interacted with other proteins, such as surfactant A (32), C (2), and D (32), integrin-␤ 1 (22), and Mac-1 (27); however, the biological role of these interactions has not been well investigated. Here, we demonstrated that inhibition of LPA 1 attenuated LPS-induced signaling pathways of phosphorylation of p38 MAPK and I-kB; however, reduction of LPA levels by overexpression of LPP1 had no effects on LPS-induced signals, indicating that LPA 1 -mediated LPS signaling is independent on its LPA-LPA 1 signaling axis in cell culture conditions.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs

Zhao

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

-Lysophosphatidic acid (LPA), a bioactive phospholipid, plays an important role in lung inflammation by inducing the release of chemokines and lipid mediators. Our previous studies have shown that LPA induces the secretion of interleukin-8 and prostaglandin E 2 in lung epithelial cells. Here, we demonstrate that LPA receptors contribute to lipopolysaccharide (LPS)-induced inflammation. Pretreatment with LPA receptor antagonist Ki16425 or downregulation of LPA receptor 1 (LPA 1) by small-interfering RNA (siRNA) attenuated LPS-induced phosphorylation of p38 MAPK, I-B kinase, and I-B in MLE12 epithelial cells. In addition, the blocking of LPA 1 also suppressed LPS-induced IL-6 production. Furthermore, LPS treatment promoted interaction between LPA 1 and CD14, a LPS coreceptor, in a time-and dose-dependent manner. Disruption of lipid rafts attenuated the interaction between LPA 1 and CD14. Mice challenged with LPS increased plasma LPA levels and enhanced expression of LPA receptors in lung tissues. To further investigate the role of LPA receptors in LPSinduced inflammation, wild-type, or LPA 1-deficient mice, or wildtype mice pretreated with Ki16425 were intratracheally challenged with LPS for 24 h. Knock down or inhibition of LPA 1 decreased LPS-induced IL-6 release in bronchoalveolar lavage (BAL) fluids and infiltration of cells into alveolar space compared with wild-type mice. However, no significant differences in total protein concentration in BAL fluids were observed. These results showed that knock down or inhibition of LPA1 offered significant protection against LPS-induced lung inflammation but not against pulmonary leak as observed in the murine model for lung injury. lysophospholipid; signal transduction; lipopolysaccharide; inflammation; acute lung injury; lysophosphatidic acid receptor 1; interleukin-6 ACUTE LUNG INJURY (ALI) is characterized by acute respiratory failure resulting from destruction of the epithelium-capillary interface, inflammation, and extravasations of protein-rich fluid (14,26,35). The lung epithelium is the site of first contact for both inflammatory and inhaled physical environmental stimuli, acting as a physical barrier between lung interstitium and environment (30,34). Disruption of epithelial barrier integrity results in paracellular leakage of relatively large proteins, such as albumin and immunoglobulin G, into alveolar spaces (15,18,19). Thus, the epithelium not only functions as a barrier but also secretes cytokines, chemokines, and lipid mediators to attract and activate a number of resident and infiltrating cells that play a role in airway inflammation (21, 25). Our previous studies have shown that bronchial epithelial cells release interleukin (IL)-8 (7, 43, 48), IL-6 (49), and prostaglandin E 2 (PGE 2 ) (17, 47) in response to bioactive lipid mediators and lipopolysaccharide (LPS), resulting in the infiltration of neutrophils into alveolar space (7, 47). The LPS-induced murine model of lung injury has been widely used to investigate mechanisms of ALI (18,31,40). Intratra...

show abstract

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs

Zhao

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…These inside-out signals can emanate from TLR2/CD14 engagement (20,22) and other receptors, such as CD44 (35). We used the mAb clone CBRM1/5 as a marker of the conformational change by the integrin to a highaffinity state (21,36). The incubation of RAW264.7 cells with 1 μM Mn 2+ induced the expected increased binding of CBRM1/5 (36) (Fig.…”

Section: Cd14 Cooperates With Cr3 To Promote Phagocytosis Of B Burgdmentioning

confidence: 99%

“…CD14 enhances CR3-mediated phagocytosis through its association with TLR2 (20)(21)(22) and involves PI3K activity (21). However, CHO cells lack a functional TLR2 (32), implying that the uptake of the spirochete by CHO-CR3/CD14 cells occurs without MyD88-mediated signaling.…”

Section: Cd14 Cooperates With Cr3 To Promote Phagocytosis Of B Burgdmentioning

confidence: 99%

“…CR3 alone is sufficient to mediate the internalization of microorganisms (19), but the participation of coreceptors, often the GPI-anchored protein CD14, may enhance phagocytosis mediated by the integrin. CD14 in combination with TLR2 induces the generation of MyD88-dependent inside-out signals that result in the activation of CR3 and its conversion to a high-affinity conformation (20)(21)(22). CR3 has been reported to mediate the nonopsonic binding of B. burgdorferi to human neutrophils and CHO cells expressing the integrin (23,24), but its contribution to the internalization of the spirochete by phagocytic cells and the mechanisms involved have not been addressed.…”

mentioning

confidence: 99%

See 1 more Smart Citation

CD14 cooperates with complement receptor 3 to mediate MyD88-independent phagocytosis ofBorrelia burgdorferi

Hawley

Olson

Iglesias-Pedraz

et al. 2012

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

View full text Add to dashboard Cite

Phagocytosis of Borrelia burgdorferi, the causative agent of Lyme disease, is a poorly understood process, despite its importance during the host immune response to infection. B. burgdorferi has been shown to bind to different receptors on the surface of phagocytic cells, including the β 2 integrin, complement receptor 3 (CR3). However, whether these receptors mediate the phagocytosis of the spirochete remains unknown. We now demonstrate that CR3 mediates the phagocytosis of the spirochete by murine macrophages and human monocytes. Interaction of B. burgdorferi with the integrin is not sufficient, however, to internalize the spirochete; phagocytosis requires the interaction of CR3 with the GPI-anchored protein, CD14, independently of TLR/MyD88-induced or inside-out signals. Interestingly, the absence of CR3 leads to marked increases in the production of TNF in vitro and in vivo, despite reduced spirochetal uptake. Furthermore, the absence of CR3 during infection with B. burgdorferi results in the inefficient control of bacterial burdens in the heart and increased Lyme carditis. Overall, our data identify CR3 as a MyD88-independent phagocytic receptor for B. burgdorferi that also participates in the modulation of the proinflammatory output of macrophages. These data also establish a unique mechanism of CR3-mediated phagocytosis that requires the direct cooperation of GPI-anchored proteins.

show abstract

“…For example, in B. anthracis, BclA-integrin interaction promotes spore uptake by macrophages in vitro (22). The exosporium contributes protection against macrophage-mediated damage (21), whereas enzymes in the exosporium (23) moderate responses to germinants.…”

mentioning

confidence: 99%

Surface architecture of endospores of the Bacillus cereus/anthracis/thuringiensis family at the subnanometer scale

Kailas

Terry

Abbott

et al. 2011

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

View full text Add to dashboard Cite

Bacteria of the Bacillus cereus family form highly resistant spores, which in the case of the pathogen B. anthracis act as the agents of infection. The outermost layer, the exosporium, enveloping spores of the B. cereus family as well as a number of Clostridia, plays roles in spore adhesion, dissemination, targeting, and germination control. We have analyzed two naturally crystalline layers associated with the exosporium, one representing the "basal" layer to which the outermost spore layer ("hairy nap") is attached, and the other likely representing a subsurface ("parasporal") layer. We have used electron cryomicroscopy at a resolution of 0.8-0.6 nm and circular dichroism spectroscopic measurements to reveal a highly α-helical structure for both layers. The helices are assembled into 2D arrays of "cups" or "crowns." High-resolution atomic force microscopy of the outermost layer showed that the open ends of these cups face the external environment and the highly immunogenic collagen-like fibrils of the hairy nap (BclA) are attached to this surface. Based on our findings, we present a molecular model for the spore surface and propose how this surface can act as a semipermeable barrier and a matrix for binding of molecules involved in defense, germination control, and other interactions of the spore with the environment.electron crystallography | cryoelectron microscopy | two-dimensional crystal

show abstract

CD14-Mac-1 interactions inBacillus anthracisspore internalization by macrophages

Cited by 78 publications

References 40 publications

Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs

Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs

CD14 cooperates with complement receptor 3 to mediate MyD88-independent phagocytosis ofBorrelia burgdorferi

Surface architecture of endospores of the Bacillus cereus/anthracis/thuringiensis family at the subnanometer scale

Contact Info

Product

Resources

About