Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Morrison, Brad; Park, Stacy J.; Mooney, Jill; Mehrad, Borna

doi:10.1172/jci18125

Cited by 189 publications

(153 citation statements)

References 55 publications

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“…However, alveolar macrophages also NK cells in the lungs (40); NK cells present in the infected area might thus interact with PMNs. Previous studies have addressed the reciprocal crosstalk of NK cells with PMNs, focusing mainly on the effects of PMNs on NK cell functions and demonstrating that PMNs favor the terminal maturation of NK cells and the acquisition of their full effector functions (6).…”

Section: Discussionmentioning

confidence: 99%

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Robinet

Baychelier

Fontaine

et al. 2014

The Journal of Immunology

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Aspergillus fumigatus is an opportunistic human fungal pathogen that sheds galactosaminogalactan (GG) into the environment. Polymorphonuclear neutrophils (PMNs) and NK cells are both part of the first line of defense against pathogens. We recently reported that GG induces PMN apoptosis. In this study, we show that PMN apoptosis occurs via a new NK cell–dependent mechanism. Reactive oxygen species, induced by the presence of GG, play an indispensable role in this apoptotic effect by increasing MHC class I chain–related molecule A expression at the PMN surface. This increased expression enables interaction between MHC class I chain–related molecule A and NKG2D, leading to NK cell activation, which in turn generates a Fas-dependent apoptosis-promoting signal in PMNs. Taken together, our results demonstrate that the crosstalk between PMNs and NK cells is essential to GG-induced PMN apoptosis. NK cells might thus play a role in the induction of PMN apoptosis in situations such as unexplained neutropenia or autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Robinet

Baychelier

Fontaine

et al. 2014

The Journal of Immunology

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“…MCP-1 expressed by epithelial and endothelial cells, fibroblasts, and macrophages is the major ligand for the C-C chemokine receptor-2 (CCR2) found on leukocytes. As shown by overexpressing MCP-1 in transgenic mice, MCP-1 recruits monocytes and natural killer cells to the lung and protects against bacterial or viral infection (26,(41)(42)(43). Although protective, overexpression of MCP-1 also causes bronchiolitis obliterans on pneumococcal challenge.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

O’Reilly

Marr

Yee

et al. 2008

Am J Respir Crit Care Med

112

124

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Rationale: Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection. Objectives: To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice. Methods: Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus. Measurements and Main Results: The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infectionassociated changes in IFN-g, IL-1b, IL-6, tumor necrosis factor-a, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1a, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis. Conclusions: These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.

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“…Isolated C57BL/6 islets treated with gliadin digest were screened using an MSD multiplex TH1/TH2 9-plex plate (data not shown). As they were highly responsive to gliadin stimulation in our screening, IL-6 and IL-10 were chosen as candidates for further investigation, along with CCL2/MCP-1, a chemokine that is produced by pancreatic islets and is known to attract monocytes, DCs, and NK cells [29][30][31][32]. We also investigated the effect of gliadin on insulin secretion in murine islets.…”

Section: Gliadin Induces Production Of Cytokines From Nk-cell-enrichementioning

confidence: 99%

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

et al. 2014

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Dietary gluten influences the development of type 1 diabetes in nonobese diabetic (NOD) mice and biobreeding rats, and has been shown to influence a wide range of immunological factors in the pancreas and gut. In the present study, the effects of gluten on NK cells were studied in vitro and in vivo. We demonstrated that gliadin increased direct cytotoxicity and IFN-γ secretion from murine splenocytes and NK cells toward the pancreatic beta-cell line MIN6 cells. Additionally, stimulation of MIN6 cells led to a significantly increased proportion of degranulating C57BL/6 CD107a + NK cells. Stimulation of C57BL/6 pancreatic islets with gliadin significantly increased secretion of IL-6 more than ninefold. In vivo, the gluten-containing diet led to a higher expression of NKG2D and CD71 on NKp46 + cells in all lymphoid organs in BALB/c and NOD mice compared with the gluten-free diet. Collectively, our data suggest that dietary gluten increases murine NK-cell activity against pancreatic beta cells. This mechanism may contribute to development of type 1 diabetes and explain the higher disease incidence associated with gluten intake in NOD mice.Keywords: C56BL/6 mice r Gliadin r Gluten r NK cells r NOD mice r Type 1 diabetes Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionDietary gluten is the initiating factor in the development of celiac disease (CD), however, an association between CD and type 1 diabetes (T1D) has been established. A gluten-free (GF) diet has been shown to have a protective effect against the development of T1D. It has been demonstrated that a GF diet in nonobese diabetic (NOD) mice reduces diabetes incidence from 64 to 15% [1], and similar results have been obtained with biobreeding rats [2]. Increased intestinal permeability occurs prior to the onset of T1D in both spontaneous animal models and human disease [3,4]. Patients with both CD and T1D diseases carry high-risk HLA alleles [5], and approximately 10% of T1D patients have anCorrespondence: Jesper Larsen e-mail: jelars@gmail.com increased prevalence of CD [6]. Moreover, T1D rarely develops after diagnosed CD, which may be because of the protective effect of a GF diet [7]. A recently published case report describes a boy with T1D who was able to maintain a low fasting blood glucose level without insulin therapy for more than 20 months after the time of diagnosis by adhering to a GF diet [8]. Lately, it has also been suggested that a family of gluten proteins known as gliadins may contribute directly to beta-cell hyperactivity, as enzymatically digested gliadin and a 33-mer gliadin fragment increase insulin secretion from beta cells by affecting the K ATP channel current [9]. This process could induce increased Ag expression of the beta-cell surface and prevent beta-cell rest [10]. Gliadin has been shown to stimulate several components of the adaptive immune system, such as Treg cells, Th17 cells, and DCs [11,12]. Gliadin fragments have also been shown to stimulate TLR4 a...

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Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Cited by 189 publications

References 55 publications

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

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