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\"A critically important and startling look at the harmful effects of overusing antibiotics, from the field's leading expert Tracing one scientist's journey toward understanding the crucial importance of the microbiome, this revolutionary book will take readers to the forefront of trail-blazing research while revealing the damage that overuse of antibiotics is doing to our health: contributing to the rise of obesity, asthma, diabetes, and certain forms of cancer. In Missing Microbes, Dr. Martin Blaser invites us into the wilds of the human microbiome where for hundreds of thousands of years bacterial and human cells have existed in a peaceful symbiosis that is responsible for the health and equilibrium of our body. Now, this invisible eden is being irrevocably damaged by some of our most revered medical advances--antibiotics--threatening the extinction of our irreplaceable microbes with terrible health consequences. Taking us into both the lab and deep into the fields where these troubling effects can be witnessed firsthand, Blaser not only provides cutting edge evidence for the adverse effects of antibiotics, he tells us what we can do to avoid even more catastrophic health problems in the future. \"-- Provided by publisher.

Mother’s milk is the best choice for infants nutrition, however when it is not available or insufficient to satisfy the needs of the infant, formula is proposed as an effective substitute. Here, we report the results of a randomized controlled clinical trial (NCT03637894) designed to evaluate the effects of two different dietary regimens (standard formula and Lactobacillus paracasei CBA L74-fermented formula) versus breastfeeding (reference group) on immune defense mechanisms (primary endpoint: secretory IgA, antimicrobial peptides), the microbiota and its metabolome (secondary outcomes), in healthy full term infants according to the type of delivery ( n  = 13/group). We show that the fermented formula, safe and well tolerated, induces an increase in secretory IgA (but not in antimicrobial peptides) and reduces the diversity of the microbiota, similarly, but not as much as, breastmilk. Metabolome analysis allowed us to distinguish subjects based on their dietary regimen and mode of delivery. Together, these results suggest that a fermented formula favors the maturation of the immune system, microbiota and metabolome. Milk breastfeeding and prebiotic-supplemented formulas have varying effects on the infant gut microbiome. Here, in a randomized controlled clinical trial, the authors investigate the effects of a Lactobacillus paracasei -fermented formula on the immune defense mechanisms, microbiota and its metabolome in full term infants.

How the Immune System Works has helped thousands of students understand what.s in their big, thick, immunology textbooks. In his book, Dr. Sompayrac cuts through the jargon and details to reveal, in simple language, the essence of this complex subject. In fifteen easy-to-read chapters, featuring the humorous style and engaging analogies developed by Dr. Sompayrac, How the Immune System Works explains how the immune system players work together to protect us from disease . and, most importantly, why they do it this way. Rigorously updated for this fifth edition, How the Immune System Works includes the latest information on subjects such as vaccines, the immunology of AIDS, and cancer. A highlight of this edition is a new chapter on the intestinal immune system . currently one of the hottest topics in immunology.

Butyrophilins (BTN) belong to the immunoglobulin (Ig) superfamily of transmembrane proteins. These molecules are of increasing interest to immunologists, as they share a structural homology with B7 family members at the extracellular domain level. Moreover, a role of these molecules has been suggested in the negative regulation of lymphocyte activation for almost all the BTN that have been studied. In addition, the expression of some BTN family members has been reported to be associated with autoimmune diseases. Over the last few years, the number of BTN and BTN-like members has greatly increased. In this study, the butyrophilin family in mammals has been revisited, using phylogenetic analysis to identify all the family members and the phylogenetic relations among them, and to establish a standard nomenclature. Fourteen BTN groups were identified that are not all conserved between mammalian species. In addition, an overview of expression profiles and functional BTN data demonstrates that these molecules represent a new area of investigation for the design of future strategies in the modulation of the immune system.

Immune function changes with ageing and is influenced by physical activity (strength training, ST) and diet (fish oil, FO). The present study investigated the effect of FO and ST on the immune system of elderly women. Forty-five women (64 ( sd 1·4) years) were assigned to ST for 90 d (ST; n 15), ST plus 2 g/d FO for 90 d (ST90; n 15) or 2 g/d FO for 60 d followed by ST plus FO for 90 d (ST150; n 15). Training was performed three times per week, for 12 weeks. A number of innate (zymosan phagocytosis, lysosomal volume, superoxide anion, peroxide of hydrogen) and adaptive (cluster of differentiation 4 (CD4), CD8, TNF-α, interferon-γ (IFN-γ), IL-2, IL-6 and IL-10 produced by lymphocytes) immune parameters were assessed before supplementation (base), before (pre-) and after (post-) training. ST induced no immune changes. FO supplementation caused increased phagocytosis (48 %), lysosomal volume (100 %) and the production of superoxide anion (32 %) and H 2 O 2 (70 %) in the ST90. Additional FO supplementation (ST150) caused no additive influence on the immune system, as ST150 and ST90 did not differ, but caused greater changes when compared to the ST ( P < 0·05). FO increased CD4 + and CD8 + lymphocytes in the ST150, which remained unchanged when training was introduced. The combination of ST and FO reduced TNF-α in the ST150 from base to post-test. FO supplementation (ST150, base–pre) when combined with exercise (ST150, pre–post) increased IFN-γ, IL-2, IL-6 and IL-10 production. The immune parameters improved in response to FO supplementation; however, ST alone did not enhance the immune system.

Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly 1 , 2 . To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1 , which encodes a crucial DNA repair protein 3 , 4 , in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence 5 – 7 in the immune system only. We show that Vav-iCre +/− ;Ercc1 −/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice 8 – 10 . Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre +/− ;Ercc1 −/fl or aged wild-type mice into young mice induced senescence in trans , whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre +/− ;Ercc1 −/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function 11 , 12 . These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing. An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.

The concept of immune privilege suggests that the central nervous system is isolated from the immune system. However, recent studies have highlighted the borders of the central nervous system as central sites of neuro-immune interactions. Although the nervous and immune systems both function to maintain homeostasis, under rare circumstances, they can develop pathological interactions that lead to neurological or psychiatric diseases. Here we discuss recent findings that dissect the key anatomical, cellular and molecular mechanisms that enable neuro-immune responses at the borders of the brain and spinal cord and the implications of these interactions for diseases of the central nervous system. Anatomical, cellular and molecular immune interactions at the borders of the central nervous system control homeostatic brain function and can lead to neurological or psychiatric diseases, representing potential therapeutic targets.

Background In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression. Methods This open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is ‘successful transplantation’, defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m 2 in stratum A and ≥ 45 ml/min per 1.73 m 2 in stratum B, after 2 years, respectively. Conclusions The OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients. Trial registration ClinicalTrials.gov: NCT03797196 , registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019.

Interactions between the immune system and the nervous system have been described mostly in the context of diseases. More recent studies have begun to reveal how certain immune cell-derived soluble effectors, the cytokines, can influence host behaviour even in the absence of infection. In this Review, we contemplate how the immune system shapes nervous system function and how it controls the manifestation of host behaviour. Interactions between these two highly complex systems are discussed here also in the context of evolution, as both may have evolved to maximize an organism’s ability to respond to environmental threats in order to survive. We describe how the immune system relays information to the nervous system and how cytokine signalling occurs in neurons. We also speculate on how the brain may be hardwired to receive and process information from the immune system. Finally, we propose a unified theory depicting a co-evolution of the immune system and host behaviour in response to the evolutionary pressure of pathogens.In this Review, Kipnis and colleagues explain how signals from the immune system can shape host behavioural responses, even in the absence of infection or disease. In particular, the authors focus on the cytokine pathways that modulate behavioural responses and consider the evolutionary basis of these neuroimmune interactions.

Recent studies indicate that cellular metabolism plays a key role in supporting immune cell maintenance and development. Here, we review how metabolism guides immune cell activation and differentiation to distinct cellular states, and how differential regulation of metabolism allows for context-dependent support during activation and lineage commitment. We discuss emerging principles of metabolic support of immune cell function in physiology and disease, as well as their general relevance to the field of cell biology. In this Review, Horng and colleagues cover the emerging roles of cellular metabolism in guiding immune cell activation and cell fate decisions, and discuss how differential metabolic regulation allows for context specificity.