Collectin-11 Is an Important Modulator of Retinal Pigment Epithelial Cell Phagocytosis and Cytokine Production

Dong, Xia; Wu, Weiju; Ma, Liang; Liu, Chengfei; Bhuckory, Mohajeet; Wang, Liping; Nandrot, Emeline F.; Xu, Heping; Li, Ké; Liu, Yizhi; Zhou, Wuding

doi:10.1159/000478042

Cited by 18 publications

(23 citation statements)

References 33 publications

(46 reference statements)

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“…Renal tubular epithelial cell were pre-incubated with FCS-free medium for 2 h and then incubated with α-mannosidase or control enzyme (β-galactosidase) (5 mM) in glycol buffer at 37°C for 1 h. FCS-containing culture medium was added to neutralize the effect of mannosidase ( 22 ). Cells were then subjected to measuring changes in Man expression and bacterial binding.…”

Section: Methodsmentioning

confidence: 99%

Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells

Song

et al. 2018

Front. Immunol.

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Recent work in a murine model of ascending urinary tract infection has suggested that C5a/C5aR1 interactions play a pathogenic role in the development of renal infection through enhancement of bacterial adhesion/colonization to renal tubular epithelial cells (RTECs). In the present study, we extended these observations to human. We show that renal tubular epithelial C5aR1 signaling is involved in promoting uropathogenic Escherichia coli (UPEC) adhesion/invasion of host cells. Stimulation of primary cultures of RTEC with C5a resulted in significant increases in UPEC adhesion/invasion of the RTEC. This was associated with enhanced expression of terminal α-mannosyl residues (Man) (a ligand for type 1 fimbriae of E. coli) in the RTEC following C5a stimulation. Mechanism studies revealed that C5aR1-mediated activation of ERK1/2/NF-κB and upregulation of proinflammatory cytokine production (i.e., TNF-α) is at least partly responsible for the upregulation of Man expression and bacterial adhesion. Clinical sample studies showed that C5aR1 and Man were clearly detected in the renal tubular epithelium of normal human kidney biopsies, and UPEC bound to the epithelium in a d-mannose-dependent manner. Additionally, C5a levels were significantly increased in urine of urinary tract infection patients compared with healthy controls. Our data therefore demonstrate that, in agreement with observations in mice, human renal tubular epithelial C5aR1 signaling can upregulate Man expression in RTEC, which enhances UPEC adhesion to and invasion of RTEC. It also suggests the in vivo relevance of upregulation of Man expression in renal tubular epithelium by C5a/C5aR1 interactions and its potential impact on renal infection.

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Section: Methodsmentioning

confidence: 99%

Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells

Song

et al. 2018

Front. Immunol.

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“…CL-11 (alias collectin-11 and CL-K1) is a pattern recognition molecule (PRM) of the lectin pathway of complement with diverse functions such as pathogen recognition, tissue homeostasis, and embryonic development ( 1 – 4 ). It is the most recently discovered member of the collectin family, mammalian C-type lectins involved in the innate immune response of the host.…”

Section: Introductionmentioning

confidence: 99%

“…During embryonic development, CL-11 is highly expressed in the craniofacial cartilage and vertebral bodies, where together with MASP-3 and CL-10, may act as a guidance cue for neural crest cell migration ( 12 ). In the mature kidney, locally-produced CL-11 appears to be critical for the development of renal injury after hypoxic and hypothermic stress ( 13 ), while in the retina local CL-11 facilitates phagocytosis of photoreceptor outer segments and modulates cytokine production in the retina ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1)

et al. 2018

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Collectin-11 (CL-11) is a pattern recognition molecule of the lectin pathway of complement with diverse functions spanning from host defense to embryonic development. CL-11 is found in the circulation in heterocomplexes with the homologous collectin-10 (CL-10). Abnormal CL-11 plasma levels are associated with the presence of disseminated intravascular coagulation, urinary schistosomiasis, and congenital disorders. Although there has been a marked development in the characterization of CL-11 there is still a scarcity of clinical tools for its analysis. Thus, we generated monoclonal antibodies and developed a quantitative ELISA to measure CL-11 in the circulation. The antibodies were screened against recombinant CL-11 and validated by ELISA and immunoprecipitation of serum and plasma. The best candidates were pairwise compared to develop a quantitative ELISA. The assay was validated regarding its sensitivity, reproducibility, and dilution linearity, demonstrating a satisfactory variability over a working range of 0.29–18.75 ng/ml. The mean plasma concentration of CL-11 in healthy controls was determined to be 289.4 ng/ml (range 143.2–459.4 ng/ml), highly correlated to the levels of CL/10/11 complexes (r = 0.729). Plasma CL-11 and CL-10/11 co-migrated in size exclusion chromatography as two major complexes of ~400 and >600 kDa. Furthermore, we observed a significant decrease at admission in CL-11 plasma levels in patients admitted to intensive care with systemic inflammatory response syndrome. By using the in-house antibodies and recombinant CL-11, we found that CL-11 can bind to zymosan independently of calcium by a separate site from the carbohydrate-binding region. Finally, we showed that CL-11/MASP-2 complexes trigger C4b deposition on zymosan. In conclusion, we have developed a specific and sensitive ELISA to investigate the ever-expanding roles of CL-11 in health and disease and shown a novel interaction between CL-11 and zymosan.

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“…Likewise, the second review article in this issue, published by Watson et al [5], is dealing with innate immune recognition. However, instead of bacteria, the focus is on viral fusion proteins which can be targeted by lung collectins such as surfactant proteins A and D. Notably, collectins are mainly discussed in terms of their antibacterial activity [2, 6] or as triggers of inflammation [7]. Therefore, the article by Watson and coworkers is highlighting another very important aspect of this class of proteins, that is their ability to clear viral pathogens.…”

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confidence: 99%

Catch Me if You Can or Actors on the Run

Egesten¹,

Herwald²

2018

J Innate Immun

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Collectin-11 Is an Important Modulator of Retinal Pigment Epithelial Cell Phagocytosis and Cytokine Production

Cited by 18 publications

References 33 publications

Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells

Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells

Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1)

Catch Me if You Can or Actors on the Run

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