The Importance of a β‐Glucan Receptor in the Nonopsonic Entry of Nontypeable<i>Haemophilus influenzae</i>into Human Monocytic and Epithelial Cells

Ahrén, Irini Lazou; Williams, David L.; Rice, Peter J.; Forsgren, Arne; Riesbeck, Kristian

doi:10.1086/322016

Cited by 65 publications

(63 citation statements)

References 38 publications

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“…It has also been reported that bGR are involved in the recognition of nontypeable Haemophilus influenzae in a variety of human cells, including monocytes and eosinophils [46,47]. The presence of Dectin-1 on both these cell types was suggestive that this receptor may be involved in the recognition of these organisms.…”

Section: Function Of the Bgr On Primary Human Macrophagesmentioning

confidence: 88%

The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

et al. 2005

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We identified the C-type-lectin-like receptor, Dectin-1, as the major receptor for fungal b-glucans on murine macrophages and have demonstrated that it plays a significant role in the cellular response to these carbohydrates. Using two novel, isoform-specific mAb, we show here that human Dectin-1, the b-glucan receptor (bGR), is widely expressed and present on all monocyte populations as well as macrophages, DC, neutrophils and eosinophils. This receptor is also expressed on B cells and a subpopulation of T cells, demonstrating that human Dectin-1 is not myeloid restricted. Both major functional bGR isoforms -bGR-A and bGR-B -were expressed by these cell populations in peripheral blood; however, only bGR-B was significantly expressed on mature monocyte-derived macrophages and immature DC, suggesting cell-specific control of isoform expression. Inflammatory cells, recruited in vivo using a new skin-window technique, demonstrated that Dectin-1 expression was not significantly modulated on macrophages during inflammation, but is decreased on recruited granulocytes. Despite previous reports detailing the involvement of other b-glucan receptors on mature human macrophages, we have demonstrated that Dectin-1 acted as the major b-glucan receptor on these cells and contributed to the inflammatory response to these carbohydrates.

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Section: Function Of the Bgr On Primary Human Macrophagesmentioning

confidence: 88%

The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

et al. 2005

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“…The goat anti-human vitronectin and fluorescein isothiocyanate (FITC)-conjugated donkey anti-goat pAbs were from Serotec (Oxford, United Kingdom). An antiserum obtained from a rabbit immunized with the clinical isolate NTHi 772 for 3 times at 2-week intervals was also included, as a control (1).…”

Section: Methodsmentioning

confidence: 99%

Binding of Complement Regulators to Invasive Nontypeable Haemophilus influenzae Isolates Is Not Increased Compared to Nasopharyngeal Isolates, but Serum Resistance Is Linked to Disease Severity

et al. 2010

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The aim of the present study was to analyze the importance of nontypeable Haemophilus influenzae (NTHi) isolated from patients with sepsis (invasive isolates) compared to nasopharyngeal isolates from patients with upper respiratory tract infection for resistance to complement-mediated attack in human serum and to correlate this result with disease severity. We studied and characterized cases of invasive NTHi disease in detail. All patients with invasive NTHi isolates were adults, and 35% had a clinical presentation of severe sepsis according to the ACCP/SCCM classification of sepsis grading. Moreover, 41% of the patients had evidence of immune deficiency. The different isolates were analyzed for survival in human serum and for binding of 125 I-labeled, purified human complement inhibitors C4b-binding protein (C4BP), factor H, and vitronectin, in addition to binding of regulators directly from serum. No significant differences were found when blood-derived and nasopharyngeal isolates were compared, suggesting that interactions with the complement system are equally important for NTHi strains, irrespective of isolation site. Interestingly, a correlation between serum resistance and invasive disease severity was found. The ability to resist the attack of the complement system seems to be important for NTHi strains infecting the respiratory tract as well as the bloodstream.

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Section: Introductionmentioning

confidence: 99%

“…19,22 Recent studies have also shown a role for dectin-1 in the phagocytosis of Haemophilus influenzae by eosinophils. 23 However, the importance of dectin-1 as a PRR and its role in promoting a proinflammatory response to a mycobacterial infection or to bacterial infections in general remains undefined.In the present study we assessed the role of various macrophage PRRs in MAPK activation and cytokine production upon mycobacterial infection. We found TLR2 and dectin-1 to work in concert to promote macrophage activation upon mycobacterial infection.…”

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confidence: 99%

The β-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria

Yadav

Schorey

2006

Blood

370

294

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Pattern recognition receptors (PRRs) play an essential role in a macrophage's response to mycobacterial infections. However, how these receptors work in concert to promote this macrophage response remains unclear. In this study, we used bone marrow-derived macrophages isolated from mannose receptor (MR), complement receptor 3 (CR3), MyD88, Toll-like receptor 4 (TLR4), and TLR2 knockout mice to examine the significance of these receptors in mediating a macrophage's response to a mycobacterial infection. We determined that mitogenactivated protein kinase (MAPK) activation and tumor necrosis factor-␣ (TNF-␣) production in macrophage infected with Mycobacterium avium or M smegmatis is dependent on myeloid differentiation factor 88 (MyD88) and TLR2 but not TLR4, MR, or CR3. Interestingly, the TLR2-mediated production of TNF-␣ by macrophages infected with M smegmatis required the ␤-glucan receptor dectin-1. A similar requirement for dectin-1 in TNF-␣ production was observed for macrophages infected with M bovis Bacillus Calmette-Guerin (BCG), M phlei, M avium 2151-rough, and M tuberculosis H37Ra. The limited production of TNF-␣ by virulent M avium 724 and M tuberculosis H37Rv was not dependent on dectin-1. Furthermore, dectin-1 facilitated interleukin-6 (IL-6), RANTES (regulated on activation, normal T expressed and secreted), and granulocyte colony-stimulating factor (G-CSF) production by mycobacteriainfected macrophages. These are the first results to establish a significant role for dectin-1, in cooperation with TLR2, to activate a macrophage's proinflammatory response to a mycobacterial infection. IntroductionThe immune system has the complex task of separating friend from foe. To accomplish this mission, the immune system has evolved receptors that recognize molecules present on pathogenic organisms but which show limited interaction with host components. These receptors, referred to as pattern recognition receptors (PRRs), function to promote an innate immune response and include such members as the mannose receptor (MR), scavenger receptors, and Toll-like receptors (TLRs), among others. PRRs bind to conserved microbial structures called pathogen-associated molecular patterns (PAMPs). The expression of these receptors allows the immune system to recognize a wide variety of pathogens that express one or more of these PAMPs, and their engagement initiates the subsequent immune response. Not surprisingly, the PRRs are expressed on cells of the innate immune system, including macrophages, neutrophils, dendritic cells, and natural killer (NK) cells. 1 Binding of microbial products by PRRs elicits a signaling response within the leukocyte, resulting in the production of specific immune modulators. Which PRRs are engaged and in what combination, along with the specific ligands involved, will dictate the overall response by the immune cell. This complexity allows the immune system to tailor its response to a specific pathogen, yet remain flexible enough to recognize a large number of potential pathogens.One of the most...

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The Importance of a β‐Glucan Receptor in the Nonopsonic Entry of NontypeableHaemophilus influenzaeinto Human Monocytic and Epithelial Cells

Cited by 65 publications

References 38 publications

The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

Binding of Complement Regulators to Invasive Nontypeable Haemophilus influenzae Isolates Is Not Increased Compared to Nasopharyngeal Isolates, but Serum Resistance Is Linked to Disease Severity

The β-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria

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