Mincle activation enhances neutrophil migration and resistance to polymicrobial septic peritonitis

Lee, Wook Bin; Yan, Jing; Kang, Ji Seon; Zhang, Quanri; Choi, Won Young; Kim, Lark Kyun; Kim, Young-Joon

doi:10.1038/srep41106

Cited by 11 publications

(5 citation statements)

References 56 publications

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“…CLR activation triggers cell adhesion, spreading, and actin polymerization ( Lee et al., 2012 , 2017 ). These processes may influence ROS production, as the regulatory components of the NADPH oxidase complex interact with the actin cytoskeleton in both resting and activated neutrophils ( el Benna et al., 1994 ; Nauseef et al., 1991 ; Woodman et al., 1991 ).…”

Section: Resultsmentioning

confidence: 99%

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation

Nguyen

Adams

et al. 2021

iScience

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Summary Signaling cascades converting the recognition of pathogens to efficient inflammatory responses by neutrophils are critical for host survival. SKAP2, an adaptor protein, is required for reactive oxygen species (ROS) generation following neutrophil stimulation by integrins, formyl peptide receptors, and for host defense against the Gram-negative bacterial pathogens, Klebsiella pneumoniae and Yersinia pseudotuberculosis . Using neutrophils from murine HoxB8-immortalized progenitors, we show that SKAP2 in neutrophils is crucial for maximal ROS response to purified C-type lectin receptor agonists and to the fungal pathogens, Candida glabrata and Candida albicans , and for robust killing of C. glabrata . Inside-out signaling to integrin and Syk phosphorylation occurred independently of SKAP2 after Candida infection. However, Pyk2, ERK1/2, and p38 phosphorylation were significantly reduced after infection with C. glabrata and K. pneumoniae in Skap2−/− neutrophils. These data demonstrate the importance of SKAP2 in ROS generation and host defense beyond antibacterial immunity to include CLRs and Candida species .

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Section: Resultsmentioning

confidence: 99%

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation

Nguyen

Adams

et al. 2021

iScience

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“…SE induced the highest influx of eosinophils and F4/80+ macrophages, whilst CAF01 induced the highest influx of neutrophils. It has been proposed that Trehalose 6,6 ′ -dimycolate (TDM), of which the immunostimulatory component of CAF01 (TDB) is a synthetic analog, can function as a neutrophil chemoattractant (39). Notably, although AH induced the lowest influx of Ly6G + neutrophils and F4/80 + macrophages of the adjuvants when measured by flow cytometry, immunohistology revealed many CD64 + cells in the injected muscle, which could be macrophages or inflammatory monocytes.…”

Section: Discussionmentioning

confidence: 99%

Vaccine Adjuvants Differentially Affect Kinetics of Antibody and Germinal Center Responses

et al. 2020

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Aluminum salts and squalene based oil-in-water emulsions (SE) are widely used adjuvants in licensed vaccines, yet their mechanisms are not fully known. Here we report that induction of antibody responses displays different kinetics dependent on the adjuvant used. SE facilitated a rapid antibody response in contrast to aluminum hydroxide (AH) and the depot-forming cationic liposome-based adjuvant (CAF01). Antigen given with the SE adjuvant rapidly reached follicular B cells in the draining lymph node, whereas antigen formulated in AH or CAF01 remained at the site of injection as a depot. Removal of the injection site early after immunization abrogated antibody responses only when antigen was given in the depot-forming adjuvants. Despite initial delays in B cell activation and germinal center (GC) formation when antigen was given in depot-forming adjuvants, the antibody levels reached higher magnitudes than when the antigen was formulated in SE. This study demonstrates that the kinetic aspect of antibody responses is critical in adjuvant benchmarking and suggests that the optimal vaccination regime depends on the adjuvant used.

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“…CLR activation triggers cell adhesion, spreading, and actin polymerization (Lee et al, 2012, Lee et al, 2017). These processes may influence ROS production, as the regulatory components of the NADPH oxidase complex interact with the actin cytoskeleton in both resting and activated neutrophils (el Benna et al, 1994, Nauseef et al, 1991, Woodman et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin andCandidastimulation

Nguyen

Xu²,

Bunnell³

et al. 2021

Preprint

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Signaling cascades that convert the recognition of pathogens to efficient inflammatory responses by immune cells, specifically neutrophils, are critical for host survival. SKAP2, an adaptor protein, is required for reactive oxygen species (ROS) generation following stimulation by integrins, formyl peptide receptors and gram-negative bacteria Klebsiella pneumoniae and Yersinia pseudotuberculosis in vitro (Nguyen et al., 2020, Shaban et al., 2020, Boras et al., 2017). SKAP2 is also required for the host defense against K. pneumoniae and Capital Greek DeltayopH Y. pseudotuberculosis infection in vivo in mouse models (Shaban et al., 2020, Nguyen et al., 2020). Another class of pattern recognition receptors (PRR) is the C-type lectin receptors (CLR), such as Dectin-1, Dectin-2 and Mincle, that are critical to trigger innate immune responses. Using neutrophils from murine HoxB8-immortalized progenitors, we show that SKAP2 is crucial for maximal ROS response to purified CLR agonists and to the fungal pathogens Candida glabrata and C. albicans, as well as for robust killing of C. glabrata. Skap2-/- murine neutrophils failed to generate ROS and exhibited reduced cellular adhesion in response to trehalose-6,6-dibehenate (TDB), furfurman, and curdlan, Mincle, Dectin-2, and Dectin-1 agonists, respectively. TDB, furfurman, and curdlan stimulation also led to SKAP2-independent integrin conformational changes, showing that inside-out signaling by these CLRs to integrin occurs in the absence of SKAP2. Pyk2 phosphorylation was significantly reduced after infection with C. glabrata in Skap2-/- neutrophils, while Syk phosphorylation was unaffected by the loss of SKAP2. These data strengthen the importance of SKAP2 in the activation of neutrophil ROS production by PRRs to include CLRs and extend the role of SKAP2 in host defense beyond antibacterial immunity to include Candida species.

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Mincle activation enhances neutrophil migration and resistance to polymicrobial septic peritonitis

Cited by 11 publications

References 56 publications

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation

Vaccine Adjuvants Differentially Affect Kinetics of Antibody and Germinal Center Responses

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin andCandidastimulation

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