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Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice.

ABSTRACT: Females are protected against mortality arising from severe sepsis; however, 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. In the present study, 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 and macrophages. The altered immune cell composition of the female peritoneum is controlled by elevated tissue chemokine expression. Female resident macrophages also exhibit greater TLR expression and enhanced phagocytosis and NADPH oxidase-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. 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.

SUBMITTER: Scotland RS

PROVIDER: S-EPMC5363818 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice.

Scotland Ramona S RS Stables Melanie J MJ Madalli Shimona S Watson Peter P Gilroy Derek W DW

Blood 20110912 22

Females are protected against mortality arising from severe sepsis; however, 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. In the present study, we show that the numbers of leukocytes occupying the na ...[more]

PMID: 21911834

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Project description:BackgroundCardiovascular disease occurs at lower incidence in premenopausal females compared with age-matched males. This variation may be linked to sex differences in inflammation. We prospectively investigated whether inflammation and components of the inflammatory response are altered in females compared with males.MethodsWe performed 2 clinical studies in healthy volunteers. In 12 men and 12 women, we assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD). In a further 8 volunteers of each sex, we assessed FMD response to glyceryl trinitrate (GTN) at baseline and at 8 hours and 32 hours after typhoid vaccine. In a separate study in 16 men and 16 women, we measured inflammatory exudate mediators and cellular recruitment in cantharidin-induced skin blisters at 24 and 72 hours.ResultsTyphoid vaccine induced mild systemic inflammation at 8 hours, reflected by increased white cell count in both sexes. Although neutrophil numbers at baseline and 8 hours were greater in females, the neutrophils were less activated. Systemic inflammation caused a decrease in FMD in males, but an increase in females, at 8 hours. In contrast, GTN response was not altered in either sex after vaccine. At 24 hours, cantharidin formed blisters of similar volume in both sexes; however, at 72 hours, blisters had only resolved in females. Monocyte and leukocyte counts were reduced, and the activation state of all major leukocytes was lower, in blisters of females. This was associated with enhanced levels of the resolving lipids, particularly D-resolvin.ConclusionsOur findings suggest that female sex protects against systemic inflammation-induced endothelial dysfunction. This effect is likely due to accelerated resolution of inflammation compared with males, specifically via neutrophils, mediated by an elevation of the D-resolvin pathway.Trial registrationClinicalTrials.gov NCT01582321 and NRES: City Road and Hampstead Ethics Committee: 11/LO/2038.FundingThe authors were funded by multiple sources, including the National Institute for Health Research, the British Heart Foundation, and the European Research Council.

Project description:BackgroundThe sex differences in memory impairment were inconclusive, and the effect of female reproductive factors (age at menarche, age at menopause, and reproductive period) on the differences was not clear. We aimed to examine the sex differences in objective and subjective memory impairment in postmenopausal women and age- and education-matched men and explore whether the differences were differed by female reproductive factors.MethodsData were obtained from the China Health and Retirement Longitudinal Study. Using the case-control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected. Memory was assessed using the three-word recall task and a self-rated question. Poisson regression models with a robust error variance were used.ResultsThe relative risk was 1.22 (95% confidence interval 1.08-1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36-1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders. The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend). It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52-53 years and having a reproductive period of 31-33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23-1.29). The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors.ConclusionsPostmenopausal women were at an increased risk of objective and subjective memory impairment than men. The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.

Dataset Information

Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice.

Publications

Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice.

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