SUMMARY Gut microbiota composition is associated with human and rodent Plasmodium infections, yet the mechanism by which gut microbiota affects the severity of malaria remains unknown. Humoral immunity is critical in mediating the clearance of Plasmodium blood stage infections, prompting the hypothesis that mice with gut microbiota-dependent decreases in parasite burden exhibit better germinal center (GC) responses. In support of this hypothesis, mice with a low parasite burden exhibit increases in GC B cell numbers and parasite-specific antibody titers, as well as better maintenance of GC structures and a more targeted, qualitatively different antibody response. This enhanced humoral immunity affects memory, as mice with a low parasite burden exhibit robust protection against challenge with a heterologous, lethal Plasmodium species. These results demonstrate that gut microbiota composition influences the biology of spleen GCs as well as the titer and repertoire of parasite-specific antibodies, identifying potential approaches to develop optimal treatments for malaria.

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Preservation of health from infectious diseases depends upon both mucosal and systemic immunity via the collaborative effort of innate and adaptive immune responses. The proficiency of host immunity stems from robust defense mechanisms—physical barriers and specialized immune cells—and a failure of these mechanisms leads to pathology. Intriguingly, immunocompetence to pathogens can be shaped by the gut microbiome as recent publications highlight a dynamic interplay between the gut microbiome and host susceptibility to infection. Modulation of host immunity to enteric pathogens has long been studied where gut bacteria shape multiple facts of both innate and adaptive immunity. Conversely, the impact of gut commensals on host immunity to extra-gastrointestinal (GI) tract infections has only recently been recognized. In this context, the gut microbiome can augment host immunity to extra-GI tract bacterial, viral, and parasitic pathogens. This review explores the research that affords insight into the role of the gut microbiome in various infectious diseases, with a particular emphasis on extra-GI tract infections. A better understanding of the link between the gut microbiome and infectious disease will be critical for improving global health in the years ahead.

Adipose tissue dysfunction is strongly linked to the development of chronic inflammation and cardiometabolic disorders in aging. While much attention has been given to the role of resident adipose tissue immune cells in the disruption of homeostasis in obesity, age-specific effects remain understudied. Here, we identified and characterized a population of γδ T cells, which show unique age-dependent accumulation in the visceral adipose tissue (VAT) of both mice and humans. Diet-induced obesity likewise increased γδ T cell numbers; however, the effect was greater in the aged where the increase was independent of fat mass. γδ T cells in VAT express a tissue-resident memory T cell phenotype (CD44hiCD62LlowCD69+) and are predominantly IL-17A-producing cells. Transcriptome analyses of immunomagnetically purified γδ T cells identified significant age-associated differences in expression of genes related to inflammation, immune cell composition, and adipocyte differentiation, suggesting age-dependent qualitative changes in addition to the quantitative increase. Genetic deficiency of γδ T cells in old age improved the metabolic phenotype, characterized by increased respiratory exchange ratio, and lowered levels of IL-6 both systemically and locally in VAT. Decreased IL-6 was predominantly due to reduced production by non-immune stromal cells, primarily preadipocytes, and adipose-derived stem cells. Collectively, these findings suggest that an age-dependent increase of tissue-resident γδ T cells in VAT contributes to local and systemic chronic inflammation and metabolic dysfunction in aging.

Objective: The objective of this study was to systematically assess the literature regarding postnatal healthcare utilization and barriers/facilitators of healthcare in neonatal abstinence syndrome (NAS) children. Methods: A systematic search was performed in PubMed, Cochrane Database of Systematic Reviews, PsychINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science to identify peer-reviewed research. Eligible studies were peer-reviewed articles reporting on broad aspects of primary and specialty healthcare utilization and access in NAS children. Three investigators independently reviewed all articles and extracted data. Study bias was assessed using the Newcastle–Ottawa Assessment Scale and the National Institute of Health Study Quality Assessment Tool. Results: This review identified 14 articles that met criteria. NAS children have poorer outpatient appointment adherence and have a higher rate of being lost to follow-up. These children have overall poorer health indicated by a significantly higher risk of ER visits, hospital readmission, and early childhood mortality compared with non-NAS infants. Intensive multidisciplinary support provided through outpatient weaning programs facilitates healthcare utilization and could serve as a model that could be applied to other healthcare fields to improve the health among this population. Conclusions: This review investigated the difficulties in accessing outpatient care as well as the utilization of such care for NAS infants. NAS infants tend to have decreased access to and utilization of outpatient healthcare following hospital birth discharge. Outpatient weaning programs have proven to be effective; however, these programs require intensive resources and care coordination that has yet to be implemented into other healthcare areas for NAS children.