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Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection.

Derebe MG, Zlatkov CM, Gattu S, Ruhn KA, Vaishnava S, Diehl GE, MacMillan JB, Williams NS, Hooper LV - Elife (2014)

Bottom Line: Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization, but their exact functions remain unclear.Mouse and human SAAs bound retinol with nanomolar affinity, were associated with retinol in vivo, and limited the bacterial burden in tissues after acute infection.Our results thus identify SAAs as a family of microbe-inducible retinol binding proteins, reveal a unique protein architecture involved in retinol binding, and suggest how retinol is circulated during infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.

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Saa1/2−/− mice have higher bacterial burdens following S. typhimurium infection.10 week old wild-type and Saa1/2−/− mice were inoculated intraperitoneally with 10,000 cfu of S. typhimurium. Livers (A) and spleens (B) were collected after 24 hr and analyzed for bacterial counts by dilution plating. Combined results from two independent experiments are shown. Each point represents one mouse and geometric means are indicated. Dotted line indicates limit of detection. **p < 0.01 using the Mann–Whitney test.DOI:http://dx.doi.org/10.7554/eLife.03206.019
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fig7: Saa1/2−/− mice have higher bacterial burdens following S. typhimurium infection.10 week old wild-type and Saa1/2−/− mice were inoculated intraperitoneally with 10,000 cfu of S. typhimurium. Livers (A) and spleens (B) were collected after 24 hr and analyzed for bacterial counts by dilution plating. Combined results from two independent experiments are shown. Each point represents one mouse and geometric means are indicated. Dotted line indicates limit of detection. **p < 0.01 using the Mann–Whitney test.DOI:http://dx.doi.org/10.7554/eLife.03206.019

Mentions: Although the precise tissue targets of circulating retinol-bound SAAs remain under investigation, several observations support the idea that SAAs promote immunity to infection. First, Saa1/2−/− mice exhibit increased susceptibility to chemically-induced colitis in mice (Eckhardt et al., 2010), suggesting that SAAs contribute to intestinal immunity. Second, studies in zebrafish show that commensal microbiota stimulate neutrophil migration through induction of SAA (Kanther et al., 2013). Third, we found that intraperitoneal infection of Saa1/2−/− mice with S. typhimurium resulted in higher bacterial loads in liver and spleen as compared to wild-type mice (Figure 7A,B), suggesting that SAAs also contribute to systemic immunity.10.7554/eLife.03206.019Figure 7.Saa1/2−/− mice have higher bacterial burdens following S. typhimurium infection.


Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection.

Derebe MG, Zlatkov CM, Gattu S, Ruhn KA, Vaishnava S, Diehl GE, MacMillan JB, Williams NS, Hooper LV - Elife (2014)

Saa1/2−/− mice have higher bacterial burdens following S. typhimurium infection.10 week old wild-type and Saa1/2−/− mice were inoculated intraperitoneally with 10,000 cfu of S. typhimurium. Livers (A) and spleens (B) were collected after 24 hr and analyzed for bacterial counts by dilution plating. Combined results from two independent experiments are shown. Each point represents one mouse and geometric means are indicated. Dotted line indicates limit of detection. **p < 0.01 using the Mann–Whitney test.DOI:http://dx.doi.org/10.7554/eLife.03206.019
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129439&req=5

fig7: Saa1/2−/− mice have higher bacterial burdens following S. typhimurium infection.10 week old wild-type and Saa1/2−/− mice were inoculated intraperitoneally with 10,000 cfu of S. typhimurium. Livers (A) and spleens (B) were collected after 24 hr and analyzed for bacterial counts by dilution plating. Combined results from two independent experiments are shown. Each point represents one mouse and geometric means are indicated. Dotted line indicates limit of detection. **p < 0.01 using the Mann–Whitney test.DOI:http://dx.doi.org/10.7554/eLife.03206.019
Mentions: Although the precise tissue targets of circulating retinol-bound SAAs remain under investigation, several observations support the idea that SAAs promote immunity to infection. First, Saa1/2−/− mice exhibit increased susceptibility to chemically-induced colitis in mice (Eckhardt et al., 2010), suggesting that SAAs contribute to intestinal immunity. Second, studies in zebrafish show that commensal microbiota stimulate neutrophil migration through induction of SAA (Kanther et al., 2013). Third, we found that intraperitoneal infection of Saa1/2−/− mice with S. typhimurium resulted in higher bacterial loads in liver and spleen as compared to wild-type mice (Figure 7A,B), suggesting that SAAs also contribute to systemic immunity.10.7554/eLife.03206.019Figure 7.Saa1/2−/− mice have higher bacterial burdens following S. typhimurium infection.

Bottom Line: Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization, but their exact functions remain unclear.Mouse and human SAAs bound retinol with nanomolar affinity, were associated with retinol in vivo, and limited the bacterial burden in tissues after acute infection.Our results thus identify SAAs as a family of microbe-inducible retinol binding proteins, reveal a unique protein architecture involved in retinol binding, and suggest how retinol is circulated during infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.

Show MeSH
Related in: MedlinePlus