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Graphical abstract Highlights • Early postnatal LB64 treatment attenuates clinical scores of colitis in adult rats. • Other treatment regimens (young adult or life-long) have no beneficial effect. • Early LB64 treatment decreases colon CD68+ cells and cytokine levels during colitis. • Early LB64 treatment boosts microbiota diversity and gut maturation in healthy rats. • Early LB64 colonisation may exert long lasting influence on immune system function. Abstract The current study investigated a potential modulating effect of orally applied Lactobacillus rhamnosus 64 (LB64) during the early postnatal period (day of life: ∼3–30), during young adult period (day of life: 31–70) or throughout experiment, on parameters of trinitrobenzenesulfonic acid (TNBS)-induced colitis in adult rats. Treatment with LB64 during early postnatal, but not during young adult period reduced clinical damage score, neutrophil and macrophage infiltration into colon, the level of cytokine and myeloperoxidase (MPO) activity, but had no influence on other parameters of oxidative damage. Early postnatal treatment with LB64 also increased the diversity of fecal Bifidobacteria and Eubacteria, and improved maturation of ileal villi in 30-days old rats. When LB64 is applied during a critical period early in life, it affects immune system functioning of adults, probably by interactions with the mucosal immune system of the gastrointestinal tract that provides immune system maturation and shapes the overall immune response. [ABSTRACT FROM AUTHOR]

Aims Some gut commensals can be protective, whereas others are implicated as necessary for development of inflammatory/autoimmune diseases. Peritoneal immune cells may play an important role in promoting autoimmunity in response to gut microbiota. This study investigated the phenotype and the function of peritoneal immune cells in the autoimmunity-resistant Albino Oxford (AO), and the autoimmunity-prone Dark Agouti (DA) rat strains upon stimulation with their own colonic E. coli or Enterococcus . Main methods Rats were intraperitoneally injected with their own E. coli or Enterococcus . Peritoneal cells isolated two days later were tested for nitric oxide (NO) and cytokine production, and for arginase and myeloperoxidase (MPO) activity. The phenotype of cells was determined using flow cytometry. Key findings While the Enterococcus injection did not affect the composition of peritoneal cells in AO rats, the E. coli treatment increased the percentages of activated CD11b int HIS48 hi neutrophils, and decreased the proportion of resident (CD11b hi HIS48 int/low , CD163 + CD86+) and anti-inflammatory CD68 + CD206+ macrophages. E. coli increased the production of NO and urea, but preserved their ratio in cells from AO rats. Conversely, both E. coli and Enterococcus diminished the proportion of resident and anti-inflammatory macrophages, increased the proportion of activated neutrophils, and induced inflammatory polarization of peritoneal cells in DA rats. However, injection of E. coli maintained the ratio of typical CD11b int HIS48 int neutrophils in DA rats, which correlated with the sustained MPO activity. Significance The rat strain differences in peritoneal cell response to own commensal microbiota may contribute to differential susceptibility to inflammatory/autoimmune diseases. [ABSTRACT FROM AUTHOR]

Abstract The systemic and extra- gonadal levels of 17β-estradiol (E2) change during aging, and affect the expression of estrogen receptors (ERs) in the immune cells of both females and males. The age-related cessation of ovarian function in females, as well as the tissue-specific expression of enzyme aromatase (estrogen synthase which significantly rises with the advancing age) in both males and females, both determine the concentration of E2 to which immune cells may be exposed. The present study was set up to investigate the direct influence of E2 in vitro on the secretory profile of peritoneal macrophages from young and naturally menopausal female rats, and from young and middle-aged male rats. The involvement of receptor(s) responsible for mediating the effects of E2 in vitro was examined by use of antagonists specific for ERα or ERβ. Whereas in macrophages from young female rats E2 treatment diminished interleukin (IL)-1β secretion, it increased it in young males, and the middle-aged females. The in vitro E2 treatment increased tumor necrosis factor (TNF)-α release by macrophages from young rats of both sexes, while it increased macrophage IL-6 release independently of both sex and age. At the same time, E2 decreased hydrogen peroxide (H 2 O 2) production in macrophages from females, and increased it in male rats of both ages, whereas it diminished nitric oxide (NO) release in all experimental groups. Inspite of the sex- and age-specific effects of E2 on macrophage urea release, E2 did not affect the NO/urea ratio in macrophages from female rats, and diminished it in macrophages from both young and middle-aged male rats. Independently of the sex and age, E2 stimulated the release of inflammatory cytokines predominantly via macrophage ERα, and inhibited the IL-1β release in young females via ERβ. In contrast, E2 increased macrophage H 2 O 2 and urea production by activating ERβ, but diminished their release via ERα. Our study may contribute to better understanding of the complex role(s) that E2 may play in innate immunity during aging, and that are dependent of sex. Highlights • E2 affects rat macrophage secretory profile in the sex- and age-specific manner. • In both sexes, E2 increased TNF-α in young, and IL-6 in young and in middle-aged. • E2 increased cytokine release via ERα but decreased IL1β in young females via ERβ. • E2 stimulated H 2 O 2 and urea release via ERβ and inhibited via ERα. • E2 reduced NO production independently of sex and age via ERα. • E2 decreased NO/Urea ratio in male rats in dose-dependent manner. [ABSTRACT FROM AUTHOR]

Rats of Albino Oxford (AO) strain in our animal facility exhibit a longer average healthy life span than rats of Dark Agouit (DA) strain. Since chronic activation of macrophages contributes to chronic low level inflammation common in older age, elucidation of the changes in middle-aged rats could be useful in prevention of unbalanced inflammatory response in advanced age. We have analysed the phenotype of unelicited and thioglycollate-elicited peritoneal macrophages from young and middle-aged DA and AO rats and tested functions of these cells following stimulation with lipopolysaccharide (LPS) in vitro. Unelicited cells from middle-aged DA rats produced higher amounts of proinflammatory mediators interleukin-6 (IL-6) and nitric oxide (NO), but have a diminished response to LPS stimulation then cells from young rats, in spite of increased frequency of TLR4- and CD14-expressing mature macrophages. Injection of thioglycollate robustly increased overall cytokine production in young rats' macrophages, while diminishing their response to LPS stimulation. In middle-aged DA rats injection of thioglycollate diminished IL-6 production, but increased it in response to LPS stimulation. Quite the contrary to DA rats, the macrophages from middle-aged AO rats have released diminished levels of TNF-α and NO, whereas urea production was strongly increased, when compared to the macrophages from young rats. Although the thioglycollate injection has increased the proportion of CD86 + MHCII + mature macrophages in young rats, and percentages of activated TLR4 + macrophages in both age groups of AO rats, it has not affected the cytokine production in young rats' macrophages, and the TNF-α production in middle-aged rats' macrophages. Moreover, the injection of thioglycollate has robustly increased the production of urea in macrophages derived from both age groups of AO rats. Although middle-aged rats of both strains were healthy during experiment, differences between the inflammatory responses of peritoneal macrophages of middle-aged rats of these strains might be one of the contributing factors defining their health in their advanced age. Development of strategies for the prevention of undesirable inflammatory changes in the elderly would benefit from the prospective study of the middle-aged. [ABSTRACT FROM AUTHOR]

The study examined the influence of sex on the alterations occurring with ageing in rat lymph node (LN) T cell compartment. In female and male rats the decrease in LN T cell counts was followed by a shift in CD4+/CD8+ T cell ratio towards CD8+ T cells, which was more prominent in males than in females. With ageing, in both major LN T cell subpopulations naïve (recent thymic emigrants and mature naïve cells) to memory/activated T cell ratio shifted to the side of memory/activated cells in female, and particularly in male rats. The frequency of regulatory CD25+Foxp3+ cells increased among LN CD4+/CD8+ T cells with ageing, reflecting, at least partly, an enhanced conversion of effector T cells into regulatory cells. This was also more prominent in male rats. The more prounounced increase in LN oxidative damage and the expression levels of proinflammatory cytokines in male rats with ageing, most likely contributed to the greater frequency of proinflammatory, replicatively senescent CD28- cells expressing CD11b (innate cell marker), among T cells of old male rats compared with age-matched females. The increase in LN oxidation/proinflammatory state with ageing was also consistent with the accumulation of exhausted PD-1high cells among T lymphocytes, particularly prominent among CD8+ T cells from male rats. Finally, by calculating a summary score for the key ageing-relevant parameters (an ageing index), a faster development of the deleterious changes in the T cell compartment occurring with ageing was confirmed in male rat LNs. Additionally, the study pointed to indices of LN T cell compartment ageing which correlate with those in peripheral blood. • Faster decline in CD4+/CD8+ T cell ratio in male than in female rat LNs with ageing • Faster erosion of the naïve T cell pool in male than in female rat LNs with ageing • Greater expansion of Tregs in male than female rat LNs with ageing • Faster development of inflammatory and oxidative damage in male rat LNs with ageing • More T cells with signs of senescence and exhaustion in male rat LNs with ageing [ABSTRACT FROM AUTHOR]