Distal Immunization and Systemic Cytokines Establish a Transient Immune Alert State in the Intestine.

Conventionally, immune responses are studied in the context of inflamed tissues and their corresponding draining lymph nodes (LNs). However, little is known about the effects of systemic inflammatory signals generated during local inflammation on distal tissues and nondraining LNs. Using a mouse model of cutaneous immunization, we found that systemic inflammatory stimuli triggered a rapid and selective distal response in the small intestine and the mesenteric LN (mesLN).

Single-cell Profiling Uncovers a -Expressing Metaplastic Gastric Cell Type Sustained by -driven Inflammation.

Unlabelled: Mechanisms for ()-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant infection and induction of constitutively active KRAS (+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that +KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin and the growth factor amphiregulin Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation.

Twice the tolerance.

A gut microbiota-derived antigen elicits distinct subsets of regulatory T cells to suppress inflammation in mice.

Pneumonia surveillance with culture-independent metatranscriptomics in HIV-positive adults in Uganda: a cross-sectional study.

Background: Pneumonia is a leading cause of death worldwide and is a major health-care challenge in people living with HIV. Despite this, the causes of pneumonia in this population remain poorly understood. We aimed to assess the feasibility of metatranscriptomics for epidemiological surveillance of pneumonia in patients with HIV in Uganda.

Distinct lung microbiota associate with HIV-associated chronic lung disease in children.

Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6-16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria.

Nourishing the Microbiota to Promote Mucosal Immunity.

Childhood undernutrition is associated with dysbiosis and dampened vaccine responses. Understanding how nutrients influence the microbiota and immunity is critical for vaccine efficacy. In this issue of Cell Host & Microbe, Di Luccia et al.

Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction.

Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients.

Role of the lung microbiome in HIV pathogenesis.

Purpose Of Review: The purpose of this review is to summarize recent findings on the lung microbiome in HIV-infected patients and associated pulmonary diseases, and the relationship of airway microbial communities to metabolic and immune signatures within this patient population.

Recent Findings: The lung microbiome in HIV infection is a relatively new and rapidly developing field; early studies in the field produced inconclusive evidence as to whether HIV-infection changes the lower airway microbiome. More recent microbiome investigations have addressed these inconsistencies by incorporating systems biology approaches and laboratory models.

Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia.

Rationale: The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown.

Objectives: To investigate whether microbiologically and immunologically distinct subsets of patients with HIV and pneumonia exist and are related to mortality.

Methods: Bronchoalveolar lavage samples from Ugandan patients with HIV and pneumonia (n = 182) were obtained at study enrollment (following antibiotic treatment); patient demographics including 8- and 70-day mortality were collected.

Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells.

Diets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by "metabolically activated" macrophages. We show that SFAs, when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion.

Human CD1a deficiency is common and genetically regulated.

CD1 proteins evolved to present diverse lipid Ags to T cells. In comparison with MHC proteins, CD1 proteins exhibit minimal allelic diversity as a result of nonsynonymous single nucleotide polymorphisms (SNPs). However, it is unknown if common SNPs in gene regulatory regions affect CD1 expression and function.