SIRT1 deficiency in myeloid cells has no effect on mortality due to gram-negative endotoxemia or gram-positive bacteremia.

<p>SIRT1 myeloid KO mice were more resistant to hypothermia in the face of LPS challenge than WT mice (A), however mortality was identical in the two groups (B; n = 5 mice per group). SIRT1 myeloid KO mice demonstrated no difference in temperature response (C) or mortality (D) due to gram-positive bacterial infection (n = 5 WT and 7 KO mice). <i>In </i><i>vivo</i> experiments were repeated twice. Data represent mean ± SD, *p < 0.05.</p

SIRT1 has minimal effects on macrophage and neutrophil antimicrobial function.

<p>Addition of a SIRT1 agonist (resveratrol) or antagonist (sirtinol) has no effect on the antimicrobial activity of the mouse derived Mφ cell line RAW 264.7 or the human derived neutrophil-like cell line HL60 (A). Lack of SIRT1 has no effect on BM-derived Mφ killing of GBS (B), but modestly decreases the ability of BM-derived Mφs to kill SPN (C). IP Mφs lacking SIRT1 demonstrate slightly decreased ability to kill SPN (D). SIRT1 deficiency does not affect alveolar Mφ antimicrobial activity (E), or change bacterial survival in whole blood (F). SIRT1 deficiency does not change the antimicrobial activity of BM neutrophils against GBS (G) or SPN (H). KO of SIRT1 in BM-derived Mφs decreases intracellular killing and phagocytosis of SPN (I). Percent bacteria killed or surviving was calculated based on initial inoculum. All conditions were done in triplicate within each assay, and each assay was repeated three times. Data represent mean ± SD, *p < 0.05, **p = 0.003, *** p < 0.001, **** p < 0.0001. </p