Inflammatory monocytes promote granuloma control of Yersinia infection.

Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined PGs, have defects in neutrophil activation and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce PGs, indicating that intestinal PGs form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores PG formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defence. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation.

Immunity to the microbiota promotes sensory neuron regeneration.

Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with neuronal interaction and repair, and promote axon growth and local nerve regeneration following injury. Mechanistically, our data reveal that the cytokine interleukin-17A (IL-17A) released by commensal-specific Th17 cells upon injury directly signals to sensory neurons via IL-17 receptor A, the transcription of which is specifically upregulated in injured neurons. Collectively, our work reveals that in the context of tissue damage, preemptive immunity to the microbiota can rapidly bridge biological systems by directly promoting neuronal repair, while also identifying IL-17A as a major determinant of this fundamental process.

Brain Glucose Hypometabolism and Iron Accumulation in Different Brain Regions in Alzheimer's and Parkinson's Diseases.

The aim of this study was to examine the relationship between the presence of glucose hypometabolism (GHM) and brain iron accumulation (BIA), two potential pathological mechanisms in neurodegenerative disease, in different regions of the brain in people with late-onset Alzheimer's disease (AD) or Parkinson's disease (PD). Studies that conducted fluorodeoxyglucose positron emission tomography (FDG-PET) to map GHM or quantitative susceptibility mapping-magnetic resonance imaging (QSM-MRI) to map BIA in the brains of patients with AD or PD were reviewed. Regions of the brain where GHM or BIA were reported in each disease were compared. In AD, both GHM and BIA were reported in the hippocampus, temporal, and parietal lobes. GHM alone was reported in the cingulate gyrus, precuneus and occipital lobe. BIA alone was reported in the caudate nucleus, putamen and globus pallidus. In PD, both GHM and BIA were reported in thalamus, globus pallidus, putamen, hippocampus, and temporal and frontal lobes. GHM alone was reported in cingulate gyrus, caudate nucleus, cerebellum, and parietal and occipital lobes. BIA alone was reported in the substantia nigra and red nucleus. GHM and BIA are observed independent of one another in various brain regions in both AD and PD. This suggests that GHM is not always necessary or sufficient to cause BIA and vice versa. Hypothesis-driven FDG-PET and QSM-MRI imaging studies, where both are conducted on individuals with AD or PD, are needed to confirm or disprove the observations presented here about the potential relationship or lack thereof between GHM and BIA in AD and PD.

Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.

The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the microbiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for heightened ERV- expression in response to commensal colonization, leading to increased immune responses and tissue inflammation. Together, our results support the idea that the host may have co-opted its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-kingdom dialog that controls both tissue homeostasis and inflammation.

Attitudes, beliefs, and norms about sex and sexuality among young Indian male adults: A qualitative study.

OBJECTIVE: Little is known about the risky sexual behaviors, attitudes, beliefs, and sources of information regarding sexual health among young adult Indian males. Currently, students in Indian secondary schools do not receive a structured comprehensive sexual health education. This qualitative study explored the sources of information, knowledge, and attitudes around sexual behaviors among young men in Mysore, India. MATERIALS AND METHODS: Between May and June 2011, 23 semi-structured qualitative in-depth interviews with males aged 18-25 years were conducted to explore their views on sexual norms, attitudes, and their sources of information to gain knowledge about sexual health. Interviews were audio recorded and transcribed verbatim. Thematic analyses were conducted. RESULTS: Participants shared a desire for quality sex education in schools but described their current sexual health curriculum as inadequate. Since social taboos dictated the space in which students gained awareness on sexual topics, the participants resorted to the outside information from both reliable and unreliable sources. CONCLUSIONS: These findings have important implications for laying the groundwork for culturally specific sexual health education interventions to meet the needs of a growing youth population in India.