tetano
Editor, Senior Moderator
Published online before print September 12, 2011, doi: 10.1182/blood-2011-03-340281 Blood September 12, 2011 blood-2011-03-340281
Sex-differences in resident immune cell phenotype underlies more efficient acute inflammatory responses in female mice
Ramona S. Scotland1,*,
Melanie J. Stables2,
Shimona Madalli1,
Peter Watson1, and
Derek W. Gilroy2
+ Author Affiliations
1 Centre for Microvascular Research, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom;
2 Department of Medicine, Rayne Institute, University College London, London, United Kingdom
↵* Corresponding author; email: r.scotland@qmul.ac.uk
Abstract
Females are protected against mortality arising from severe sepsis. The precise mechanisms that confer this survival advantage in females over males are unclear. Resident leukocytes in resting tissues have a significant influence on circulating cytokine levels and recruitment of blood leukocytes during acute inflammatory responses. Whether the phenotype of resident leukocytes is distinct in females is unknown. Herein we show that the numbers of leukocytes occupying the naive peritoneal and pleural cavities is higher in female than in male mice and rats, comprising more T- and B-lymphocytes as well as macrophages. The altered immune cell composition of the female peritoneum is controlled by elevated tissue chemokine expression. Female resident macrophages also exhibit greater Toll-like receptor expression, as well as enhanced phagocytosis and NADPHoxidase-mediated bacterial killing. However, macrophage-derived cytokine production is diminished by proportionally more resident immunomodulatory CD4+ T-lymphocytes. Ovarian hormones regulate macrophage phenotype, function, and numbers but have no significant impact on T-lymphocyte populations in females. Thus we have identified a fundamental sex-difference in phenotype of resident leukocytes. We propose that the distinct resident leukocyte population in females allows aggressive recognition and elimination of diverse infectious stimuli without recruitment of circulating neutrophils or excessive cytokine production.
http://bloodjournal.hematologylibra...ract?sid=03b65776-193b-4e3c-a545-013e34959567
Sex-differences in resident immune cell phenotype underlies more efficient acute inflammatory responses in female mice
Ramona S. Scotland1,*,
Melanie J. Stables2,
Shimona Madalli1,
Peter Watson1, and
Derek W. Gilroy2
+ Author Affiliations
1 Centre for Microvascular Research, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom;
2 Department of Medicine, Rayne Institute, University College London, London, United Kingdom
↵* Corresponding author; email: r.scotland@qmul.ac.uk
Abstract
Females are protected against mortality arising from severe sepsis. The precise mechanisms that confer this survival advantage in females over males are unclear. Resident leukocytes in resting tissues have a significant influence on circulating cytokine levels and recruitment of blood leukocytes during acute inflammatory responses. Whether the phenotype of resident leukocytes is distinct in females is unknown. Herein we show that the numbers of leukocytes occupying the naive peritoneal and pleural cavities is higher in female than in male mice and rats, comprising more T- and B-lymphocytes as well as macrophages. The altered immune cell composition of the female peritoneum is controlled by elevated tissue chemokine expression. Female resident macrophages also exhibit greater Toll-like receptor expression, as well as enhanced phagocytosis and NADPHoxidase-mediated bacterial killing. However, macrophage-derived cytokine production is diminished by proportionally more resident immunomodulatory CD4+ T-lymphocytes. Ovarian hormones regulate macrophage phenotype, function, and numbers but have no significant impact on T-lymphocyte populations in females. Thus we have identified a fundamental sex-difference in phenotype of resident leukocytes. We propose that the distinct resident leukocyte population in females allows aggressive recognition and elimination of diverse infectious stimuli without recruitment of circulating neutrophils or excessive cytokine production.
http://bloodjournal.hematologylibra...ract?sid=03b65776-193b-4e3c-a545-013e34959567