Direct Bacterial Killing In Vitro by Recombinant Nod2 Is Compromised by Crohn's Disease-Associated Mutations

Perez, Laurent; Butler, Margaret H.; Creasey, Tammy; Dzink-Fox, JoAnn; Gounarides, John S.; Petit, S.; Ropenga, Anna; Ryder, Neil S.; Smith, Kathryn L.; Smith, Philip; Parkinson, Scott J.

doi:10.1371/journal.pone.0010915

Cited by 16 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior studies demonstrated that NOD2 is an essential mediator of host defense against a variety of intracellular pathogens such as Listeria monocytogenes (56), Mycobacterium tuberculosis (23,54), and Legionella pneumophila (9). In addition, it has been demonstrated that murine macrophages require NOD2 to respond to Staphylococcus aureus infection (31).…”

mentioning

confidence: 99%

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

Theivanthiran¹,

Batra²,

Balamayooran³

et al. 2012

Infect Immun

View full text Add to dashboard Cite

Bacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs against Escherichia coli, the individual roles of NOD1 and NOD2 in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen, E. coli. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2 ؊/؊ mice following E. coli infection. Furthermore, we observed reduced activation of NF-B and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2 ؊/؊ mice upon E. coli challenge. Moreover, NOD2؊/؊ neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2 ؊/؊ mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2 ؊/؊ mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2؊/؊ mice demonstrate a reduction in activation of NF-B and MAPKs similar to that seen with NOD2 ؊/؊ mice in response to E. coli. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation.

show abstract

mentioning

confidence: 99%

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

Theivanthiran¹,

Batra²,

Balamayooran³

et al. 2012

Infect Immun

View full text Add to dashboard Cite

show abstract

“…• Dysbiosis was confirmed in uninvolved HS skin by 3 teams. 6,76,77 • An immune deficiency towards commensal gut flora was reported in patients with Crohn's disease carrying a NOD2 mutation, 78 while some HS patients can present with both diseases.…”

Section: Furthermorementioning

confidence: 99%

What causes hidradenitis suppurativa ?—15 years after

Zouboulis

Benhadou

Byrd

et al. 2020

Experimental Dermatology

119

View full text Add to dashboard Cite

show abstract

“…Their expression is normally associated with myeloid and non-lymphoid cell types. Upon ‘sensing’ these ligands via leucine rich repeat domains (LRR)(3, 4), dimerization occurs via the oligomerization domain, leading to caspase-recruitment domain (CARD) dependent interaction with the serine threonine kinase RIP2 (Receptor interacting protein 2) (5–7). The peptidoglycan ligand activated NOD: RIP2 complex promotes the potent activation of NFκB, leading to the production of inflammatory mediators and chemokines (8).…”

Section: Introductionmentioning

confidence: 99%

The Bacterial Peptidoglycan-Sensing Molecules NOD1 and NOD2 Promote CD8+ Thymocyte Selection

Martinic

Caminschi

O’Keeffe

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Nucleotide-binding and oligomerization domain (NOD)-like receptors NOD1 and NOD2 are cytosolic innate immune receptors that recognize microbial peptidoglycans. Whilst studies have addressed the role of NOD proteins in innate immune responses, little attention has been given to their impact on the developing adaptive immune system. We have assessed the roles of NOD1 and NOD2 deficiency on T cell development in mice. Our results demonstrate that NOD1 and NOD2 promote the positive selection/maturation of CD8 SP thymocytes in a thymocyte intrinsic manner. TCR-mediated ERK phosphorylation is significantly reduced in the absence of NOD proteins, but RIP2 is not involved in CD8 SP thymocyte selection or ERK signaling. Commensal bacteria free animals have thymocyte maturation defects and exogenous NOD ligands can enhance thymocyte maturation in culture. These results raise the intriguing possibility that abnormal lymphocyte responses observed in NOD-dependent inflammatory diseases are not driven solely by microbial signals in the gut, but may also involve intrinsic lymphocyte defects resulting from impaired CD8 T cell thymic development.

show abstract

Direct Bacterial Killing In Vitro by Recombinant Nod2 Is Compromised by Crohn's Disease-Associated Mutations

Cited by 16 publications

References 40 publications

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

What causes hidradenitis suppurativa ?—15 years after

The Bacterial Peptidoglycan-Sensing Molecules NOD1 and NOD2 Promote CD8+ Thymocyte Selection

Contact Info

Product

Resources

About