O-017 HIF-mediated Autophagy Contributes to Intestinal Epithelial Cell-intrinsic Innate Immune Response Against Invasive Bacteria

We have previously demonstrated that mice exposed to sublethal hyperoxia (an atmosphere of >95% oxygen for 4 days, followed by return to room air) have significantly impaired pulmonary innate immune response. Alveolar macrophages (AM) from hyperoxia-exposed mice exhibit significantly diminished antimicrobial activity and markedly reduced production of inflammatory cytokines in response to stimulation with LPS compared with AM from control mice in normoxia. As a consequence of these defects, mice exposed to sublethal hyperoxia are more susceptible to lethal pneumonia with Klebsiella pneumoniae than control mice. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a growth factor produced by normal pulmonary alveolar epithelial cells that is critically involved in maintenance of normal AM function. We now report that sublethal hyperoxia in vivo leads to greatly reduced alveolar epithelial cell GM-CSF expression. Systemic treatment of mice with recombinant murine GM-CSF during hyperoxia exposure preserved AM function, as indicated by cell surface Toll-like receptor 4 expression and by inflammatory cytokine secretion following stimulation with LPS ex vivo. Treatment of hyperoxic mice with GM-CSF significantly reduced lung bacterial burden following intratracheal inoculation with K. pneumoniae, returning lung bacterial colony-forming units to the level of normoxic controls. These data point to a critical role for continuous GM-CSF activity in the lung in maintenance of normal AM function and demonstrate that lung injury due to hyperoxic stress results in significant impairment in pulmonary innate immunity through suppression of alveolar epithelial cell GM-CSF expression.

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Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response in BALB/c mice and in primary intestinal epithelial cell culture involving toll-like receptors TLR-2 and TLR-4

European Journal of Nutrition ◽

10.1007/s00394-015-0832-2 ◽

2015 ◽

Vol 55 (1) ◽

pp. 139-146 ◽

Cited By ~ 10

Author(s):

Jean-François Mallet ◽

Émilie Graham ◽

Barry W. Ritz ◽

Kohei Homma ◽

Chantal Matar

Keyword(s):

Cell Culture ◽

Immune Response ◽

Epithelial Cell ◽

Intestinal Epithelial Cell ◽

Intestinal Epithelial ◽

Toll Like Receptors ◽

Epithelial Cell Culture

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Shigella interaction with intestinal epithelial cells determines the innate immune response in shigellosis

International Journal of Medical Microbiology ◽

10.1078/1438-4221-00244 ◽

2003 ◽

Vol 293 (1) ◽

pp. 55-67 ◽

Cited By ~ 19

Author(s):

M. Isabel Fernandez ◽

Philippe J. Sansonetti

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Innate Immune Response ◽

Intestinal Epithelial Cells ◽

Innate Immune ◽

Intestinal Epithelial

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Lactobacillus delbrueckii CRL 581 Differentially Modulates TLR3-Triggered Antiviral Innate Immune Response in Intestinal Epithelial Cells and Macrophages

Microorganisms ◽

10.3390/microorganisms9122449 ◽

2021 ◽

Vol 9 (12) ◽

pp. 2449

Author(s):

Mariano Elean ◽

Leonardo Albarracin ◽

Kohtaro Fukuyama ◽

Binghui Zhou ◽

Mikado Tomokiyo ◽

...

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Innate Immune Response ◽

Intestinal Epithelial Cells ◽

Starter Culture ◽

Innate Immune ◽

Lactobacillus Delbrueckii ◽

Poly I:C ◽

Intestinal Epithelial ◽

Antiviral Immune Response

Lactobacillus delbrueckii subsp. lactis CRL 581 beneficially modulates the intestinal antiviral innate immune response triggered by the Toll-like receptor 3 (TLR3) agonist poly(I:C) in vivo. This study aimed to characterize further the immunomodulatory properties of the technologically relevant starter culture L. delbrueckii subsp. lactis CRL 581 by evaluating its interaction with intestinal epithelial cells and macrophages in the context of innate immune responses triggered by TLR3. Our results showed that the CRL 581 strain was able to adhere to porcine intestinal epithelial (PIE) cells and mucins. The CRL 581 strain also augmented the expression of antiviral factors (IFN-α, IFN-β, Mx1, OAS1, and OAS2) and reduced inflammatory cytokines in PIE cells triggered by TLR3 stimulation. In addition, the influence of L. delbrueckii subsp. lactis CRL 581 on the response of murine RAW macrophages to the activation of TLR3 was evaluated. The CRL 581 strain was capable of enhancing the expression of IFN-α, IFN-β, IFN-γ, Mx1, OAS1, TNF-α, and IL-1β. Of note, the CRL 581 strain also augmented the expression of IL-10 in macrophages. The results of this study show that the high proteolytic strain L. delbrueckii spp. lactis CRL 581 was able to beneficially modulate the intestinal innate antiviral immune response by regulating the response of both epithelial cells and macrophages relative to TLR3 activation.

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