CD200 Modulates S. aureus-Induced Innate Immune Responses Through Suppressing p38 Signaling

Zhu, Bo; Yu, Yingying; Liu, Xiaoyi; Qin, Han; Kang, Yanhua; Shi, Liyun

doi:10.3390/ijms20030659

Cited by 11 publications

(14 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activating CD200/ CD200R signaling may be insufficient to contain the NF-κB pathway after stroke in vivo. Recent studies reported that the CD200/CD200R pathway modulated the inflammatory response by controlling MAPK activation in vitro and in vivo [49][50][51]. The current results showed that CD200Fc inhibited MAPK activation by suppressing the phosphorylation of p-JNK and p-p38 after stroke.…”

Section: Discussionsupporting

confidence: 56%

The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke

Sun

Xia

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Spontaneous functional recovery occurs during the acute phase after stroke onset, but this intrinsic recovery remains limited. Therefore, exploring the mechanism underlying spontaneous recovery and identifying potential strategies to promote functional rehabilitation after stroke are very important. The CD200/CD200R signaling pathway plays an important role in neurological recovery by modulating synaptic plasticity during multiple brain disorders. However, the effect and mechanism of action of the CD200/CD200R pathway in spontaneous functional recovery after stroke are unclear.Methods: In this study, we used a transient middle cerebral artery occlusion (MCAO) model in rats to investigate the function of CD200/CD200R signaling in spontaneous functional recovery after stroke. We performed a battery of behavioral tests (Longa test, adhesive removal test, limb-use asymmetry test, and the modified grip-traction test) to evaluate sensorimotor function after intracerebroventricular (i.c.v.) injection with CD200 fusion protein (CD200Fc) or CD200R blocking antibody (CD200R Ab) post-stroke. Density and morphology of dendritic spines were analyzed by Golgi staining. Microglia activation was evaluated by immunofluorescence staining. Western blot was used to detect the levels of protein and the levels of mRNA were measured by qPCR. Results: Our study demonstrated that sensorimotor function, synaptic proteins, and structures were gradually recovered and CD200R was transiently upregulated in ipsilateral cortex after stroke. Synapse-related proteins and dendritic spines were preserved, accompanied by sensorimotor functional recovery, after stereotaxic CD200Fc injection post-stroke. In addition, CD200Fc restrained microglia activation and pro-inflammatory factor release (such as Il-1, Tnf-α, and Il-6) after MCAO. On the contrary, CD200R Ab aggravated sensory function recovery in adhesive removal test and further promoted microglia activation and pro-inflammatory factor release (such as Il-1) after MCAO. The immune-modulatory effect of CD200/CD200R signaling might be exerted partly by its inhibition of the MAPK pathway. Conclusions:This study provides evidence that the CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity via inhibition of microglia activation and inflammatory factor release.

show abstract

Section: Discussionsupporting

confidence: 56%

The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke

Sun

Xia

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…In steady-state lung, AMs are in an immunosuppressed state and their phenotype is tightly control by the lung microenvironment. They express high level of CD200 receptor (CD200R) which is associated with M2 phenotype ( 42 , 43 ) and are involved in the downregulation of immune inflammation ( 44 , 45 ). This may be important for tolerating innocuous inhaled agent.…”

Section: Amsmentioning

confidence: 99%

Cross-Talk Between Alveolar Macrophages and Lung Epithelial Cells is Essential to Maintain Lung Homeostasis

Bissonnette

Lauzon-Joset

Debley³

et al. 2020

Front. Immunol.

146

109

View full text Add to dashboard Cite

The main function of the lung is to perform gas exchange while maintaining lung homeostasis despite environmental pathogenic and non-pathogenic elements contained in inhaled air. Resident cells must keep lung homeostasis and eliminate pathogens by inducing protective immune response and silently remove innocuous particles. Which lung cell type is crucial for this function is still subject to debate, with reports favoring either alveolar macrophages (AMs) or lung epithelial cells (ECs) including airway and alveolar ECs. AMs are the main immune cells in the lung in steady-state and their function is mainly to dampen inflammatory responses. In addition, they phagocytose inhaled particles and apoptotic cells and can initiate and resolve inflammatory responses to pathogens. Although AMs release a plethora of mediators that modulate immune responses, ECs also play an essential role as they are more than just a physical barrier. They produce anti-microbial peptides and can secrete a variety of mediators that can modulate immune responses and AM functions. Furthermore, ECs can maintain AMs in a quiescent state by expressing anti-inflammatory membrane proteins such as CD200. Thus, AMs and ECs are both very important to maintain lung homeostasis and have to coordinate their action to protect the organism against infection. Thus, AMs and lung ECs communicate with each other using different mechanisms including mediators, membrane glycoproteins and their receptors, gap junction channels, and extracellular vesicles. This review will revisit characteristics and functions of AMs and lung ECs as well as different communication mechanisms these cells utilize to maintain lung immune balance and response to pathogens. A better understanding of the cross-talk between AMs and lung ECs may help develop new therapeutic strategies for lung pathogenesis.

show abstract

“…Cd200r1 encodes a cell surface glycoprotein that downregulates pro-inflammatory signaling ( 29 , 46 ). Additionally, Chen et al showed that CD200, the ligand of CD200R1, triggers phagocytosis ( 47 ).…”

Section: Resultsmentioning

confidence: 99%

“…We explain these discrepancies with the higher cellular complexity of PCLS in which individual and cell-type specific dependencies may be masked. The involvement of CD200R1 in the uptake of live P. aeruginosa was surprising knowing its well-established function as inhibitor of pro-inflammatory signaling ( 29 , 46 , 68 ). Our first assumption that heat-killed P. aeruginosa is not able to overcome the limiting actions of CD200R1 reflecting in a diminished pro-inflammatory cytokine profile did not prove as being true.…”

Section: Discussionmentioning

confidence: 99%

Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine Precision Cut Lung Slices Depends on Sensing of Bacterial Viability

Kolbe¹,

Yi²,

Poth³

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Breathing allows a multitude of airborne microbes and microbial compounds to access the lung. Constant exposure of the pulmonary microenvironment to immunogenic particles illustrates the need for proper control mechanisms ensuring the differentiation between threatening and harmless encounters. Discrimination between live and dead bacteria has been suggested to be such a mechanism. In this study, we performed infection studies of murine precision cut lung slices (PCLS) with live or heat-killed P. aeruginosa , in order to investigate the role of viability for induction of an innate immune response. We demonstrate that PCLS induce a robust transcriptomic rewiring upon infection with live but not heat-killed P. aeruginosa . Using mutants of the P. aeruginosa clinical isolate CHA, we show that the viability status of P. aeruginosa is assessed in PCLS by TLR5-independent sensing of flagellin and recognition of the type three secretion system. We further demonstrate that enhanced cytokine expression towards live P. aeruginosa is mediated by uptake of viable but not heat-killed bacteria. Finally, by using a combined approach of receptor blockage and genetically modified PCLS we report a redundant involvement of MARCO and CD200R1 in the uptake of live P. aeruginosa in PCLS. Altogether, our results show that PCLS adapt the extent of cytokine expression to the viability status of P. aeruginosa by specifically internalizing live bacteria.

show abstract

CD200 Modulates S. aureus-Induced Innate Immune Responses Through Suppressing p38 Signaling

Cited by 11 publications

References 40 publications

The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke

The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke

Cross-Talk Between Alveolar Macrophages and Lung Epithelial Cells is Essential to Maintain Lung Homeostasis

Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine Precision Cut Lung Slices Depends on Sensing of Bacterial Viability

Contact Info

Product

Resources

About