Mannose-Containing Molecular Patterns Are Strong Inducers of Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Macrophages

Fernández, Nieves; Alonso, Sara; Valera, Isela; Vigo, Ana G.; Renedo, Marta; Barbolla, L; Crespo, Mariano Sánchez

doi:10.4049/jimmunol.174.12.8154

Cited by 47 publications

(36 citation statements)

References 63 publications

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“…The MR recognizes glycosylated molecules with terminal mannose, fucose, and N-acetylglucosamine moieties (50). Its role in pathogen-triggered signaling is beginning to be appreciated (51). Nigou et al (23) have reported that Saccharomyces cerevisiae mannan could inhibit LPS-induced IL-12 release from dendritic cells.…”

Section: Specific Down-regulation Of Irak-m Abolishes the Inhibitory mentioning

confidence: 99%

Mycobacterium tuberculosis Lipoarabinomannan-mediated IRAK-M Induction Negatively Regulates Toll-like Receptor-dependent Interleukin-12 p40 Production in Macrophages

Pathak¹,

Basu

Bhattacharyya

et al. 2005

Journal of Biological Chemistry

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Mycobacterum tuberculosis is the causative agent of tuberculosis, which leads to an estimated 2 to 3 million deaths worldwide each year. The organism evades the immune response of the host by manipulating host cell signaling pathways (1). One of the important mechanisms is the suppression of interleukin-12 (IL-12) 3 production. IL-12 is a heterodimeric cytokine composed of two disulfide-linked subunits of 35 (p35) and 40 (p40) kDa encoded by two separate genes (2-4). It is produced by macrophages and dendritic cells in response to infection with bacteria or exposure to bacterial constituents such as lipopolysaccharide (LPS) (2, 4). It is required for cell-mediated immunity and host defense against intracellular microbes (5). IL-12 is critical for the generation of Th1 responses against M. tuberculosis infection. In support of this view are the observations that individuals with mutations affecting the genes of IL-12 (6) or its receptor (7,8) have increased susceptibility to mycobacterial infections. IL-12-deficient mice are susceptible to Mycobacterium bovis bacillus Calmette-Guerin infection (9). This underscores the need to understand how M. tuberculosis dampens IL-12 production. Intracellular bacteria and bacterial products regulate IL-12 production at the transcriptional level (10). The best studied transcriptional regulation of the IL-12 p40 promoter is mediated by binding of Rel family members effecting induction of a Th1 immune response (11-13). We therefore considered the possibility of M. tuberculosis modulins dampening this pathway.Lipoarabinomannan (LAM) is a cell wall lipoglycan. LAMs have been considered modulins because of their capacity to manipulate the host immune system. To date, three families of LAMs have been described (14). A glycosylphosphatidylinositol anchor, a D-mannan core, and a large terminal D-arabinan represents the core structure. The arabinan domain is capped by either mannosyl (15-18) or phosphoinositol residues (19,20). The mannose-capped LAMs (Man-LAMs) are found in pathogenic species including M. tuberculosis (14). Phosphoinositol-capped LAMs have been isolated from non-pathogenic species such as Mycobacterium smegmatis. Phosphoinositol-capped LAMs activate macrophages in a Toll-like receptor (TLR) 2-dependent manner by activating NF-B-dependent pathways (21). Mycobacterial Man-LAMs on the other hand, modulate the immune response by dampening IL-12 production in macrophages and dendritic cells (22,23) and attenuating apoptotic signaling (24,25). The emerging consensus is that Man-LAM contributes to the capacity of M. tuberculosis to survive inside macrophages by mediating immunosuppressive effects. Recent studies have demonstrated that lipomannans induce IL-12 production (26) in a TLR-dependent manner and may also inhibit IL-12 production in a TLR-independent manner (27), suggesting that the ratio of lipomannans to Man-LAM may govern the capacity of the organism to circumvent IL-12 production. The anti-inflammatory effects of Man-LAM have been attributed to their binding to t...

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Section: Specific Down-regulation Of Irak-m Abolishes the Inhibitory mentioning

confidence: 99%

Mycobacterium tuberculosis Lipoarabinomannan-mediated IRAK-M Induction Negatively Regulates Toll-like Receptor-dependent Interleukin-12 p40 Production in Macrophages

Pathak¹,

Basu

Bhattacharyya

et al. 2005

Journal of Biological Chemistry

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“…In previous studies, we have observed a robust release of AA in human monocytes (10) and polymorphonuclear leukocytes (PMN) (11) by two pathogen-associated molecular signatures, namely, peptidoglycan (PGN) and mannose-based polymers, thus defining pathogen-associated molecular patterns as chief stimuli for AA metabolism. In the present study, we addressed the effect of a set of stimuli acting through receptors involved in recognition of microbial components by DC.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Costimulation of Dectin-1 and DC-SIGN Triggers the Arachidonic Acid Cascade in Human Monocyte-Derived Dendritic Cells

Valera

Fernández

Trinidad

et al. 2008

The Journal of Immunology

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Inflammatory mediators derived from arachidonic acid (AA) alter the function of dendritic cells (DC), but data regarding their biosynthesis resulting from stimulation of opsonic and nonopsonic receptors are scarce. To address this issue, the production of eicosanoids by human monocyte-derived DC stimulated via receptors involved in Ag recognition was assessed. Activation of FcγR induced AA release, short-term, low-grade PG biosynthesis, and IL-10 production, whereas zymosan, which contains ligands of both the mannose receptor and the human β-glucan receptor dectin-1, induced a wider set of responses including cyclooxygenase 2 induction and biosynthesis of leukotriene C4 and IL-12p70. The cytosolic phospholipase A2 inhibitor pyrrolidine 1 completely inhibited AA release stimulated via all receptors, whereas the spleen tyrosine kinase (Syk) inhibitors piceatannol and R406 fully blocked AA release in response to immune complexes, but only partially blocked the effect of zymosan. Furthermore, anti-dectin-1 mAb partially inhibited the response to zymosan, and this inhibition was enhanced by mAb against DC-specific ICAM-3-grabbing nonintegrin (SIGN). Immunoprecipitation of DC lysates showed coimmunoprecipitation of DC-SIGN and dectin-1, which was confirmed using Myc-dectin-1 and DC-SIGN constructs in HEK293 cells. These data reveal a robust metabolism of AA in human DC stimulated through both opsonic and nonopsonic receptors. The FcγR route depends on the ITAM/Syk/cytosolic phospholipase A2 axis, whereas the response to zymosan involves the interaction with the C-type lectin receptors dectin-1 and DC-SIGN. These findings help explain the distinct functional properties of DC matured by immune complexes vs those matured by β-glucans.

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“…It belongs to a family of fungal immunogenic MPs and stimulates a high production of specific antibodies (Viudes et al 2001). The main mechanism by which the MP produces the modulation of the immune response is related to mannose receptors present on dendritic cells (Mansour et al 2006;Fernández et al 2005). However, the protein portion of mannoproteins has an intrinsic capacity to stimulate a potent immune response (Pietrella et al 2008;La Valle et al 2000).…”

Section: Resultsmentioning

confidence: 99%

Saccharomyces uvarum mannoproteins stimulate a humoral immune response in mice

Darpossolo

Eto

Venâncio

et al. 2012

Braz. arch. biol. technol.

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Yeasts discarded in industrial processes can be used as a nutritional supplement and to extract cellular components with biotechnological aims. In this study, the humoral immune response of Swiss mice treated with mannoproteins (MP) from the yeast Saccharomyces uvarum was evaluated. The mice were treated with MPs at different doses and times and inoculated with 2% sheep red blood cells. An increase in total Ig in mice treated with 100 µg of MP at the time of immunization or 24 h before was observed in the primary

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Mannose-Containing Molecular Patterns Are Strong Inducers of Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Macrophages

Cited by 47 publications

References 63 publications

Mycobacterium tuberculosis Lipoarabinomannan-mediated IRAK-M Induction Negatively Regulates Toll-like Receptor-dependent Interleukin-12 p40 Production in Macrophages

Mycobacterium tuberculosis Lipoarabinomannan-mediated IRAK-M Induction Negatively Regulates Toll-like Receptor-dependent Interleukin-12 p40 Production in Macrophages

Costimulation of Dectin-1 and DC-SIGN Triggers the Arachidonic Acid Cascade in Human Monocyte-Derived Dendritic Cells

Saccharomyces uvarum mannoproteins stimulate a humoral immune response in mice

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