Cholesterol-rich domains are involved in Bordetella pertussis phagocytosis and intracellular survival in neutrophils

Lamberti, Yanina Andrea; Vidakovics, Laura Perez; Pol, Ludo-W. Van der; Rodrı́guez, Marı́a Eugenia

doi:10.1016/j.micpath.2008.01.002

Cited by 32 publications

(37 citation statements)

References 40 publications

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“…Although LTs enhance phagocytosis of microbes via a myriad of opsonic or pathogen recognition receptors, 38 41 and Naroeni and Porte 42 reported that M␤CD failed to interfere with ingestion of IgG-opsonized pathogens in neutrophils and J774.A1 cells, respectively. In our model, cholesterol depletion had no impact on baseline Fc␥R-mediated phagocytosis or bacterial killing.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the role of LRs in opsonic phagocytosis is controversial. Kwiatkowska et al showed that LRs are important for the ingestion of IgG-coated targets in U937 cells, 20 whereas Lamberti et al 41 and Naroeni and Porte 42 reported that M␤CD failed to interfere with ingestion of IgG-opsonized pathogens in neutrophils and J774.A1 cells, respectively. In our model, cholesterol depletion had no impact on baseline Fc␥R-mediated phagocytosis or bacterial killing.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, such dependency on LR integrity was not observed for the antimicrobial effects mediated by an alternative class of LT receptor, CysLT1. Our findings using both biochemical and imaging approaches represent the first examples of which we are aware of (1) GPCR redistribution to LRs upon engagement of an immunoreceptor, and (2) a direct interaction between a GPCR and an immunoreceptor.Although LTs enhance phagocytosis of microbes via a myriad of opsonic or pathogen recognition receptors, 38 41 and Naroeni and Porte 42 reported that M␤CD failed to interfere with ingestion of IgG-opsonized pathogens in neutrophils and J774.A1 cells, respectively. In our model, cholesterol depletion had no impact on baseline Fc␥R-mediated phagocytosis or bacterial killing.…”

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confidence: 99%

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FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions

Serezani

Aronoff

Sitrin

et al. 2009

Blood

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IntroductionMacrophages play a central role in antimicrobial immunity via their capacities for recognition, phagocytosis, and killing of opsonized and nonopsonized microbes. Nowhere are these functions more vigorously tested than in the lung, which comprises the largest internal interface with the outside environment and which is continuously exposed to microbes delivered via inhalation or oropharyngeal aspiration. 1 Particles opsonized by immunoglobulin (Ig)G antibodies bind to receptors recognizing the Fc portion of IgG (Fc␥ receptor [Fc␥R]). 2 There are 3 general classes of Fc␥R (Fc␥RI, II, and III) that vary in their molecular structure, affinity for different IgG isotypes, signal transduction, and phagocyte effector functions. 3 Not all Fc␥R classes are capable of eliciting phagocytosis. 3 In the human pulmonary alveolar macrophage (AM), Fc␥RI is the most abundantly expressed class of phagocytic Fc␥Rs, but low levels of Fc␥RIIa are also detected. 4 On Fc␥R clustering, its immunoreceptor tyrosine-based activation motif (ITAM) is phosphorylated by receptor-associated protein tyrosine kinases (PTKs) of the Src family (Src, Lck, Lyn, Fgr, Hck, Fyn, and Yes). The phosphorylated ITAM then serves as a docking site for Src-homology 2 domain-containing adapter proteins and enzymes, including Syk PTK, phospholipase C, the Ras-activating enzyme Sos, and phosphoinositide 3-kinase. 5 Upon their engagement by IgG-opsonized targets, both Fc␥Rs as well as some of their associated signaling molecules redistribute to lipid rafts (LRs), highly dynamic cholesterol-and sphingolipid-enriched microdomains that can act as platforms on which signaling proteins are assembled and which serve to compartmentalize a variety of cellular processes. 6 In addition to their roles in the membrane reorganization events of phagocytosis, these signaling molecules are also required for the induction of proinflammatory mediators involved in the amplification of phagocyte actions as well as the recruitment of leukocytes to the inflammatory milieu. 7 Among such mediators, the 5-lipoxygenase-derived products of arachidonic acid, leukotriene (LT) B 4 , and the cysteinyl LTs (CysLTs), LTC 4 , LTD 4 , and LTE 4 , enhance a myriad of leukocyte functions. 8 LTB 4 and CysLTs each bind 2 different classes of G protein-coupled receptors (GPCRs), termed leukotriene B 4 receptors 1 and 2 (BLT1 and BLT2) 9,10 and CysLT receptors 1 and 2 (CysLT1 and CysLT2). 11,12 GPCRs signal through the activation of small heterotrimeric G proteins that modulate the generation of second messengers, such as cyclic adenosine 5Ј-monophosphate and Ca 2ϩ . 13 We have shown that exogenously added or endogenously generated LTB 4 and LTD 4 promote Fc␥R-dependent phagocytosis and microbial killing in AMs via BLT1 and CysLT1, respectively; 14,15 however, there are key differences in the intracellular programs they use to enhance AM functions. First, LTB 4 / BLT1 is a more potent enhancer of AM phagocytosis and bacterial killing of IgG-opsonized targets than is LTD 4 /CysLT1. 16 Second,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions

Serezani

Aronoff

Sitrin

et al. 2009

Blood

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“…However, the specifics of the involvement of DRMs in phagocytosis remain unclear. Phagocytosis of nonopsonized mycobacteria or Bordetella pertussis by neutrophils was inhibited by depletion of cholesterol in contrast to that of serum-opsonized zymosan or bacteria (27,28).…”

Section: Recipient Of a Canadian Arthritis Network Graduate Award Andmentioning

confidence: 94%

FcγRIIIb Triggers Raft-dependent Calcium Influx in IgG-mediated Responses in Human Neutrophils

Marois¹,

Paré

Vaillancourt

et al. 2011

Journal of Biological Chemistry

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Human neutrophils constitutively express a unique combination of Fc␥Rs, namely Fc␥RIIa and Fc␥RIIIb. Numerous lines of evidence support the concept that these Fc␥Rs generate only partially characterized intracellular signals. However, despite the fact that both receptors are likely to be engaged simultaneously in a physiological setting, no recent publications have investigated the distinct, although partially convergent, results of their joint activation in IgG-dependent responses. To examine the significance of the co-expression of Fc␥RIIa and Fc␥RIIIb on human neutrophils, we analyzed the neutrophil responses to stimuli that engage these Fc␥Rs, namely the phagocytosis of human IgG-opsonized zymosan and the responses to heat-aggregated IgGs. Blocking antibodies to either Fc␥R significantly decreased the phagocytic index and the stimulated production of superoxide anions. Both receptors are required for optimal IgG-dependent responses by human neutrophils. On the other hand, only blocking antibodies to Fc␥RIIIb, but not to Fc␥RIIa, inhibited the mobilization of calcium in response to heat-aggregated IgGs. Furthermore, phagocytosis of IgG-opsonized zymosan by human neutrophils required an extracellular influx of calcium that was blocked only by antibodies against Fc␥RIIIb. We also observed that this calcium influx as well as the IgG-dependent phagocytosis were dependent on the integrity of the plasma membrane detergent-resistant microdomains to which both isoforms were recruited following stimulation by heat-aggregated IgGs. These data clarify the mechanisms that regulate the Fc␥Rs constitutively expressed on human neutrophils, describe a specific contribution of Fc␥RIIIb at the level of the mobilization of calcium, and provide evidence for a crucial role of detergent-resistant microdomains in this process.

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“…96,114 Nevertheless, a theoretical shortcoming of Th2-polarized immune response would be the inability to clear intracellular pathogens as is the case with non-opsonized B. pertussis phagocytosed by human macrophages in vitro 115 or in vivo 116 and neutrophils. 117 In the absence of a memory Th1 response, an infection would have the potential to become persistent despite the absence of acute symptoms in humans or an apparent clearance of bacteria from the respiratory tract of animals. This has been supported by an observation that the co-administration of IL-12 with an acellular vaccine, which induced a shift in bias from a Th2 to Th1 response, enhanced the rate of clearance following a bacterial challenge.…”

Section: History Of Whooping Cough Prophylaxismentioning

confidence: 99%

Development of improved vaccines against whooping cough: Current status

Marzouqi¹,

Richmond²,

Fry³

et al. 2010

Human Vaccines

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Cholesterol-rich domains are involved in Bordetella pertussis phagocytosis and intracellular survival in neutrophils

Cited by 32 publications

References 40 publications

FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions

FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions

FcγRIIIb Triggers Raft-dependent Calcium Influx in IgG-mediated Responses in Human Neutrophils

Development of improved vaccines against whooping cough: Current status

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