NO Is a Macrophage Autonomous Modifier of the Cytokine Response to Streptococcal Single-Stranded RNA

Deshmukh, S. D.; Müller, Sabrina; Hese, Katrin; Rauch, Katharina S.; Wennekamp, Julia; Takeuchi, Osamu; Akira, Shizuo; Golenbock, Douglas T.; Henneke, Philipp

doi:10.4049/jimmunol.1101383

Cited by 17 publications

(16 citation statements)

References 28 publications

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“…Blocking phagocytosis by the mycotoxin CytD resulted in a significant drop in levels of secreted IL6 (Fig. 5 B ), confirming the previously reported dependence of cytokine formation on the uptake of bacteria (17, 20). Notably, when phagocytosis was blocked, which was confirmed by FACS analysis (Supplemental Fig.…”

Section: Resultssupporting

confidence: 89%

The endolysosomal cysteine cathepsins L and K are involved in macrophage‐mediated clearance of Staphylococcus aureus and the concomitant cytokine induction

et al. 2013

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Cysteine cathepsins are endolysosomal cysteine proteases highly expressed in macrophages; however, their individual contributions to the elimination of bacteria and bacteria-induced cytokine production by macrophages are unknown. We assessed the contribution of cysteine cathepsins to macrophage defense pathways against Staphylococcus aureus by using chemical inhibitors and by infecting primary bone marrow-derived macrophages deficient in 1 of 7 major macrophage-expressed endolysosomal cysteine proteases. We show that cysteine cathepsins are involved in the phagocytosis and killing of S. aureus. Cathepsin L was identified as an executor of nonoxidative killing. Moreover, microarray data revealed cysteine cathepsins to be important for the maximal induction of certain proinflammatory genes, such as IL6, in response to S. aureus. Cysteine cathepsin's contribution to IL6 production was dependent on phagocytosis, and cathepsin K was identified to be a critical protease in this process. Analysis of macrophages with impaired trafficking of endolysosomal Toll-like receptors (TLRs) to the acidic compartment revealed that they were not involved in cathepsin-dependent IL6 induction. Because IL6 production was completely dependent on the TLR-adaptor protein myeloid differentiation primary response gene 88 (MyD88), it appears that other TLRs are involved. In summary, lysosomal cysteine proteases are functionally linked to the complex bactericidal and inflammatory activities of macrophages.

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Section: Resultssupporting

confidence: 89%

The endolysosomal cysteine cathepsins L and K are involved in macrophage‐mediated clearance of Staphylococcus aureus and the concomitant cytokine induction

et al. 2013

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“…Also, type I interferons (IFNs) and IFN- γ , IL-6, IL-12, and IL-18 contribute significantly to the course of GBS neonatal sepsis [153, 154]. The recognition of GBS and other Gram-positive bacteria by macrophages and monocytes relies on bacterial single-stranded RNA and phagocytosis induced NO in a Myd88 and UNC-93B-dependent manner but independently of known nucleotide-sensing TLRs [155, 156]. Recently, the activation of NLRP3 inflammasome, leading to production of IL-1 β and IL-18, was also shown to be involved in host defenses against this pathogen [157].…”

Section: Neonatal Innate Immune Response Infections and Sepsismentioning

confidence: 99%

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Tourneur

Chassin

2013

Clinical and Developmental Immunology

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The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis. Contact with potent immunostimulatory molecules starts immediately at birth, and the discrimination between commensal bacteria and invading pathogens is essential to avoid an inappropriate immune stimulation and/or host infection. The dysregulation of these tight interactions between host and microbiota can be responsible for important health disorders, including inflammation and sepsis. This review summarizes the molecular events leading to the establishment of postnatal immune tolerance and how pathogens can avoid host immunity and induce neonatal infections and sepsis.

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“…Initial studies indicated that infection of murine macrophages and DCs with live S. agalactiae resulted in MyD88-dependent production of proinflammatory cytokines like TNF and IL-1b, but it did not require receptors classically involved in the sensing of Grampositive bacteria (i.e., TLR2, TLR7, or TLR9) (68,69). Dependency on bacterial internalization, phagosomal acidification, and Unc93B1 (27, 68) indicated a predominant role for the nucleic acid-sensing pathways in the recognition of S. agalactiae by an unidentified MyD88-dependent receptor.…”

Section: Significance Of Bacterial Rna Recognition For Innate Immune mentioning

confidence: 99%

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

Eigenbrod

Dalpke

2015

The Journal of Immunology

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Although DNA of bacterial and viral origin, as well as viral RNA, have been intensively studied as triggers of innate immune responses, the stimulatory properties of bacterial RNA and its role during infections have just begun to be deciphered. Bacterial RNA is a strong inducer of type I IFN and NF-κB–dependent cytokines, and it also can activate the Nlrp3 inflammasome. In this review, we focus on the receptors and signaling pathways involved in innate immune activation by bacterial RNA and analyze the physiological relevance of bacterial RNA recognition during infections. Furthermore, we present the concept that RNA modifications can impair RNA-dependent immune activation. RNA modifications differ between eukaryotes and prokaryotes; thus, they can serve to define the innate pattern that is recognized. In this regard, we discuss the role of ribose 2′-O-methylation as a potential immune-escape mechanism.

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NO Is a Macrophage Autonomous Modifier of the Cytokine Response to Streptococcal Single-Stranded RNA

Cited by 17 publications

References 28 publications

The endolysosomal cysteine cathepsins L and K are involved in macrophage‐mediated clearance of Staphylococcus aureus and the concomitant cytokine induction

The endolysosomal cysteine cathepsins L and K are involved in macrophage‐mediated clearance of Staphylococcus aureus and the concomitant cytokine induction

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

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