Systemic Immune Function Research Articles

Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function.

Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques. PBio therapy resulted in significantly increased frequencies of B cells expressing IgA in the colon and lymph node (LN), likely because of significantly increased LN T follicular helper cell frequencies and LN follicles. Increased frequencies of IL-23(+) APCs in the colon were found post-PBio treatment, which correlated with LN T follicular helper cells. Finally, VSL#3 significantly downmodulated the response of TLR2-, TLR3-, TLR4-, and TLR9-expressing HEK293 cells to stimulation with Pam3CSK4, polyinosinic-polycytidylic acid, LPS, and ODN2006, respectively. These data provide a mechanism for the beneficial impact of PBio on mucosal health and implicates the use of PBio therapy in the context of vaccination or preventative approaches to enhance protection from mucosal infection by improving immune defenses at the mucosal portal of entry.

The Microbiome, Systemic Immune Function, and Allotransplantation.

Diverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future.

Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-Positive T cells expressing IL-1 receptor type 2 and regulatory T Cells

BackgroundAccumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear.ResultsWe have shown that age-related developments of T-cell dysfunction, hearing loss, and degeneration of cochlear spiral ganglion (SG) neurons observed in 6-month-old mice were recovered in 12 months old mice which previously given fetal thymus transplants twice. We have also demonstrated that CD4+ T cells expressing interleukin 1 receptor type 2 (IL-1R2) and naturally occurring regulatory T cells (nTregs), which expanded in aged 12-month-old mice, were reduced in the thymus-grafted mice of the same age.ConclusionIt is conceivable that the rejuvenation of systemic immune function by fetal thymus grafts contributes not only to the activation of cellular immunity but also to the decrease of IL-1R2+ CD4+ T cells or nTregs, which cells accelerate both age-related hearing loss (AHL) and neurodegeneration of the cochlear neurons. Further studies on the interactions among IL-1R2 expression on CD4+ T cells, Tregs, and neuronal cells and also on the relationships between fetal thymus grafting and the rejuvenation of systemic immunity should be designed in order to advance towards therapeutic effects on neurosenescence, including AHL.

Dermal white adipose tissue: a new component of the thermogenic response

Recent literature suggests that the layer of adipocytes embedded in the skin below the dermis is far from being an inert spacer material. Instead, this layer of dermal white adipose tissue (dWAT) is a regulated lipid layer that comprises a crucial environmental defense. Among all the classes of biological molecules, lipids have the lowest thermal conductance and highest insulation potential. This property can be exploited by mammals to reduce heat loss, suppress brown adipose tissue activation, reduce the activation of thermogenic programs, and increase metabolic efficiency. Furthermore, this layer responds to bacterial challenge to provide a physical barrier and antimicrobial disinfection, and its expansion supports the growth of hair follicles and regenerating skin. In sum, this dWAT layer is a key defensive player with remarkable potential for modifying systemic metabolism, immune function, and physiology. In this review, we discuss the key literature illustrating the properties of this recently recognized adipose depot.

Bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: role in osteoclast-mediated NK cell activation.

The aim of this study is to establish osteoclasts as key immune effectors capable of activating the function of Natural Killer (NK) cells, and expanding their numbers, and to determine in vivo and in vitro effect of bisphosphonates (BPs) during NK cell interaction with osteoclasts and on systemic and local immune function. The profiles of 27 cytokines, chemokines and growth factors released from osteoclasts were found to be different from dendritic cells and M1 macrophages but resembling to untreated monocytes and M2 macrophages. Nitrogen-containing BPs Zoledronate (ZOL) and Alendronate (ALN), but not non-nitrogen-containing BPs Etidronate (ETI), triggered increased release of pro-inflammatory mediators from osteoclasts while all three BPs decreased pit formation by osteoclasts. ZOL and ALN mediated significant release of IL-6, TNF-` and IL-1β, whereas they inhibited IL-10 secretion by osteoclasts. Treatment of osteoclasts with ZOL inhibited NK cell mediated cytotoxicity whereas it induced significant secretion of cytokines and chemokines. NK cells lysed osteoclasts much more than their precursor cells monocytes, and this correlated with the decreased expression of MHC class I expression on osteoclasts. Intravenous injection of ZOL in mice induced pro-inflammatory microenvironment in bone marrow and demonstrated significant immune activation. By contrast, tooth extraction wound of gingival tissues exhibited profound immune suppressive microenvironment associated with dysregulated wound healing to the effect of ZOL which could potentially be responsible for the pathogenesis of Osteonecrosis of the Jaw (ONJ). Finally, based on the data obtained in this paper we demonstrate that osteoclasts can be used as targets for the expansion of NK cells with superior function for immunotherapy of cancer.

Intestinal microflora and allergic diseases in children

Intestinal microflora play a significant role in regulating systemic immune function, maintaining the intestinal barrier, and preventing the invasion of external pathogenic bacteria.Recent epidemiological studies and experimental research suggest that the occurrence and development of allergic diseases is associated with the disturbances in the intestinal microflora during early life.Research has been taken to evaluate the prevention and treatment effects in allergic disease of probiotics, which is currently unestablished. Key words: Intestinal microflora; Allergic disease; Probiotics; Children

Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort.

Patients with chronic obstructive pulmonary disease (COPD) who are defined as frequent exacerbators suffer with 2 or more exacerbations every year. The molecular mechanisms responsible for this phenotype are poorly understood. We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort. Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR) testing. Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01) between frequent compared to non-exacerbators. In sputum cells, only 6 genes were differentially expressed. The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes. Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10. The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively. There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations.

Defects in host immune function in tree frogs with chronic chytridiomycosis.

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has caused mass mortality leading to population declines and extinctions in many frog species worldwide. The lack of host resistance may be due to fungal immunosuppressive effects that have been observed when Bd is incubated with cultured lymphocytes, but whether in vivo host immunosuppression occurs is unknown. We used a broad range of hematologic and protein electrophoresis biomarkers, along with various functional tests, to assess immune competence in common green (Litoria caerulea) and white-lipped (L. infrafrenata) tree frogs experimentally infected with Bd. Compared with uninfected frogs, Bd infection in L. caerulea caused a reduction in immunoglobulin and splenic lymphocyte responses to antigenic stimulation with sheep red blood cells, along with decreased white blood cell and serum protein concentrations, indicating possible impaired immune response capability of Bd-infected frogs. This is the first in vivo study suggesting that infection with Bd causes multiple defects in systemic host immune function, and this may contribute to disease development in susceptible host species. Although L. infrafrenata failed to maintain Bd infection after exposure, white blood cell and serum globulin concentrations were lower in recovered frogs compared with unexposed frogs, but antigen-specific serum and splenic antibody, and splenic cellular, responses were similar in both recovered and unexposed frogs. This may indicate potential systemic costs associated with infection clearance and/or redirection of host resources towards more effective mechanisms to overcome infection. No clear mechanism for resistance was identified in L. infrafrenata, suggesting that localized and/or innate immune defense mechanisms may be important factors involved in disease resistance in this species.

Keratinocyte antiviral response to Poly(dA:dT) stimulation and papillomavirus infection in a canine model of X-linked severe combined immunodeficiency.

X-linked severe combined immunodeficiency (XSCID) is caused by a genetic mutation within the common gamma chain (γc), an essential component of the cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. XSCID patients are most commonly treated with bone marrow transplants (BMT) to restore systemic immune function. However, BMT-XSCID humans and dogs remain at an increased risk for development of cutaneous papillomavirus (PV) infections and their associated neoplasms, most typically cutaneous papillomas. Since basal keratinocytes are the target cell for the initial PV infection, we wanted to determine if canine XSCID keratinocytes have a diminished antiviral cytokine response to poly(dA:dT) and canine papillomavirus-2 (CPV-2) upon initial infection. We performed quantitative RT-PCR for antiviral cytokines and downstream interferon stimulated genes (ISG) on poly(dA:dT) stimulated and CPV-2 infected monolayer keratinocyte cultures derived from XSCID and normal control dogs. We found that XSCID keratinocytes responded similarly to poly(dA:dT) as normal keratinocytes by upregulating antiviral cytokines and ISGs. CPV-2 infection of both XSCID and normal keratinocytes did not result in upregulation of antiviral cytokines or ISGs at 2, 4, or 6 days post infection. These data suggest that the antiviral response to initial PV infection of basal keratinocytes is similar between XSCID and normal patients, and is not the likely source for the remaining immunodeficiency in XSCID patients.

Intestinal dendritic cells in the regulation of mucosal immunity.

The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.

Different cellular responses of dexmedetomidine at infected site and peripheral blood of emdotoxemic BALB/c mice.

Various sedative agents, including dexmedetomidine (dex), induce immunosuppression, and enhance infection progression. However, there was no information on how anesthetic affects local and systemic cellular immune function. We conducted this study to examine the impact of dex on the differentiation and function of immune cells at site of inflammation and in peripheral blood during endotoxemia of mice. In BALB/c mice with and without endotoxemia, we evaluated the influence of two dosages of 5 and 50 mcg/kg/h intravenous dex on immune cells: including number of T cells (CD3), B cells (CD19), natural killer cells (CD8a), monocytes (CD11b), and macrophages (Mac-3) in peripheral blood, the activities of macrophages in peripheral blood and in peritoneal lavage, and proliferation of B and T cells and of natural killer cells activity in the spleen. Endotoxemia increased the number of CD3 T cells, CD 19 B cells and macrophages in the peripheral blood, augmented macrophage activity in the peritoneum, and increased T cell proliferation and natural killer cell activity in the spleen. Further administration of 5 mcg/kg/h dex attenuated systemic increase in number of T cells, B cells, and macrophages during endotoxemia and 50 mcg/kg/h dex significantly attenuated the increase in activity of macrophages in the peripheral blood during endotoxemia. In the peritoneum, however, 5 mcg/kg/h dex preserved and 50 mcg/kg/h dexmedetomidine enhanced the activity of macrophages during endotoxemia. Increased in proliferation of T cells in spleen during endotoxemia was attenuated by both doses of dex. Last, 50 mcg/kg/h dex enhanced natural killer cells activity during endotoxemia. While preserving the effects of endotoxemia on macrophage's activity in the infection site and natural killer cell's activity in the spleen, dex decreased systemic fulminant immune reaction in endotoxemia, by attenuating the augmented response in the number of T cells, B cells and macrophages, activity of macrophages in the peripheral blood, and proliferation of T cells in spleen during endotoxemia.

A role for hormones, gut microbiota and tolerogenic CD103DC in protection of male (NZBxNZW)F1 (BWF1) mice from lupus (MUC8P.805)

Abstract Mechanisms leading to gut homeostasis affect both mucosal and systemic immune function, and involve gut microbiota. Tolerogenic dendritic cells (CD103DC) play a role in gut homeostasis, including generation of induced regulatory T cells (iTregs). Previously, we found that treatment of male BWF1 mice with anti-CD103 antibody significantly increases disease incidence/mortality. Male CD103DC exhibit significantly greater tolerogenic function than either female or castrated male CD103DC in vitro. This study examines the mechanism of sex differences in CD103DC function, and the role of microbiota in lupus. Sex differences in CD103DC function correlated with increased expression of genes associated with tolerogenic/anti-inflammatory function in males, and pro-inflammatory function in females, and changes in iTreg frequency and function in vivo. Male BWF1 CD103DC expressed more Raldh2, an enzyme required for retinoic acid (RA) synthesis and CD103DC function, and supplementation with RA restored tolerogenic function in female CD103DC. Further, we found that male gut microbiota differed significantly from adult, but not immature, female microbiota, suggesting hormones influence the gut microbiota. Importantly, transfer of male gut microbiota to female BWF1 mice significantly reduced anti-dsDNA antibody production. These data suggest that an interplay between hormones, gut microbiota and tolerogenic CD103DC may play a critical role in providing protection to male BWF1 mice.

The role of the probiotic Bifidobacterium animalis subsp. lactis on systemic immune function in humans (382.7)

Evidence suggests that probiotic bacteria modulate both innate and adaptive immunity; however the immune response varies by type of organism. Probiotics in the genera Bifidobacterium may stimulate T cell and cytokine responses that augment cell mediated immunity. The goal of the current study was to evaluate the effect of one species, Bifidobacterium animalis subsp. lactis BB‐12 at a dose of log 10 ± 0.5 CFUs/day on immune responses in a controlled, 4‐period crossover, free‐living study. Furthermore, the matrix used to deliver probiotic bacteria may influence the performance and efficacy of probiotic interventions in vivo. Therefore, a sub‐aim of this project will determine if the immune response to BB‐12 differs depending on the delivery matrix of the probiotic bacteria. Healthy adults (n=27) aged 18‐40 years old with BMI 20‐35 kg/m2 were recruited, and received 4 treatments in a random order: 1) yogurt smoothie alone; smoothie with organism added 2) before or 3) after fermentation, or 4) organism given in tablet form. At baseline and after each treatment, peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood, and functional and phenotypic marker expression was assessed. The distribution of immune cell subsets (e.g. T and B lymphocytes, nature killer cells, dendritic cells, macrophages and granulocytes) in peripheral blood was not altered by any treatment However, we observed a treatment effect on TNF‐α and IL‐6 secretion from BB‐12 (p=0.027) and LPS stimulated PBMCs and on T cell proliferation (p=0.036). This interim analysis suggests that probiotic treatment may be altering the immune response in humans, and the delivery matrix of BB‐12 also influences its performance in vivo.Grant Funding Source: Supported by Dairy Research Instituite

Xylo-oligosaccharides alone or in synbiotic combination withBifidobacterium animalissubsp.lactisinduce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25-65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.

The microbiome and asthma.

That the subglottic airways are not sterile, as was once believed, but are populated by a distinct "bronchial microbiome," is now accepted. Also accepted is the concept that asthma is associated with differences in the composition of this microbiome. What is not clear is whether the differences in microbial community composition themselves mediate pathologic changes in the airways or whether they reflect differences in systemic immune function driven by differences in the development of the gastrointestinal microbiome in early life, when the immune system is most malleable. Recognition of the probable existence of a "common mucosal immune system" allowed synthesis of these apparently opposing ideas into a single conceptual model. Gastrointestinal microbiome-driven differences in systemic immune function predispose to sensitization to allergens deposited on mucosal surfaces, whereas possibly similar, but not identical, differences in immune function predispose to less effective responses to microbial infection of the airways, resulting in persistence of the inflammation underlying the structural and functional abnormalities of asthma. In this model, allergic sensitization and asthma are thus seen as commonly overlapping but not necessarily coincident consequences of abnormalities in microbial colonization, development of immune function, and encounter with agents infecting the respiratory tract.

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

Sitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.

Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis.

Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by TNBS were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi and clinical, immunological and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared to vehicle controls. Treated groups were pyrexic, but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of IL-1β, IL-6 and TNF-α, while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1α deficient mice, strongly implicating epithelial HIF-1α as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis.

Dietary fat quality in regular fat diets has minor effects on biomarkers of inflammation in obese Zucker rats

Adipose tissue-associated chronic inflammation is involved in the pathogenesis of obesity-related diseases. Dietary fatty acids are known to influence inflammatory processes. The aim of this study was to investigate, whether diets with regular fat contents but variable fat qualities affect adipose tissue-associated inflammation through the fatty acid composition of mesenteric adipose tissue (MAT). Obese Zucker rats were fed diets containing 7 % wt:wt rapeseed oil, corn oil, or lard for 10 weeks. Fatty acid composition and endocrine function regarding adipokines and cytokines of MAT, number of total CD3(+) T cells, and cytokine secretion of mesenteric lymph node (MLN)-derived lymphocytes were determined. Local effects in MAT and MLN were compared to systemic effects assessed in serum and peripheral blood mononuclear cells. Fatty acid composition of MAT reflected dietary fatty acid intake, without affecting endocrine function. Feeding the lard diet for 10 weeks increased the serum adiponectin and TNF-α secretion of blood lymphocytes, whereas CD3(+) T cells in blood were decreased. No effects were seen for the secretion of adipokines and cytokines from MAT, the amount of T cells in MLN, and cytokine secretion of MLN lymphocytes. In conclusion, feeding obese rats a diet with regular fat content but variable fat sources for 10 weeks, changed the fatty acid composition of MAT but not its secretory properties or MLN functions. Although the local immune system was not influenced, lard-feeding induced minor changes in systemic immune function.

Barrier Immune Effectors Are Maintained during Transition from Nurse to Forager in the Honey Bee

Foragers facilitate horizontal pathogen transmission in honey bee colonies, yet their systemic immune function wanes during transition to this life stage. In general, the insect immune system can be categorized into mechanisms operating at both the barrier epithelial surfaces and at the systemic level. As proposed by the intergenerational transfer theory of aging, such immunosenescence may result from changes in group resource allocation. Yet, the relative influence of pathogen transmission and resource allocation on immune function in bees from different stages has not been examined in the context of barrier immunity. We find that expression levels of antimicrobial peptides (AMPs) in honey bee barrier epithelia of the digestive tract do not follow a life stage-dependent decrease. In addition, correlation of AMP transcript abundance with microbe levels reveals a number of microbe-associated changes in AMPs levels that are equivalent between nurses and foragers. These results favor a model in which barrier effectors are maintained in foragers as a first line of defense, while systemic immune effectors are dismantled to optimize hive-level resources. These findings have important implications for our understanding of immunosenescence in honey bees and other social insects.

Postoperative Immunosuppression After Open and Laparoscopic Liver Resection: Assessment of Cellular Immune Function and Monocytic HLA-DR Expression

Major abdominal procedures are strongly associated with postoperative immunosuppression and subsequent increased patient morbidity. It is believed that laparoscopic surgery causes less depletion of the systemic immune function because of the reduced tissue trauma. Various cytokines and monocytic HLA-DR expression have been successfully implemented to assess postoperative immune function. The aim of our study was to show the difference in immunologic profiles after minimally invasive versus conventional liver resection. Ten animals underwent either laparoscopic or conventional open left lateral liver resection. Flow cytometric characteristics of HLA-DR expression on monocytes and lipopolysaccharide-stimulated cellular secretion of tumor necrosis factor α, interferon γ, interleukin 6, and interleukin 8 were measured and analyzed in ex vivo whole blood samples. Intraoperative and postoperative clinical outcome parameters were also documented and evaluated. All animals survived the procedures. Postoperative complications were fever (n = 3), wound infections (n = 2), and biloma (n = 1). Open surgery showed a morbidity rate of 80% compared with 40% after laparoscopic surgery. Laparoscopic liver resection showed no postoperative immunoparalysis. Major histocompatibility complex class II expression in this group was elevated, whereas the open surgery group showed decreased major histocompatibility complex class II expression on postoperative day 1. Postoperative secretion of tumor necrosis factor , interleukin 6, and interferon was lower in the open surgery group. Elevated transaminase levels after laparoscopy might have resulted from an ischemia/reperfusion injury caused by the capnoperitoneum. Major immunoparalysis depression was not observed in either group. Laparoscopic surgery shows a tendency to improve immunologic recovery after liver resection.