Critical Role of Macrophages and Their Activation via MyD88-NFκB Signaling in Lung Innate Immunity to Mycoplasma pneumoniae

Mycoplasma pneumoniae (Mp), a common cause of pneumonia, is associated with asthma; however, the mechanisms underlying this association remain unclear. We investigated the cellular immune response to Mp in mice. Intranasal inoculation with Mp elicited infiltration of the lungs with neutrophils, monocytes and macrophages. Systemic depletion of macrophages, but not neutrophils, resulted in impaired clearance of Mp from the lungs. Accumulation and activation of macrophages were decreased in the lungs of MyD88−/− mice and clearance of Mp was impaired, indicating that MyD88 is a key signaling protein in the anti-Mp response. MyD88-dependent signaling was also required for the Mp-induced activation of NFκB, which was essential for macrophages to eliminate the microbe in vitro. Thus, MyD88-NFκB signaling in macrophages is essential for clearance of Mp from the lungs

Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection

Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC) into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease

Nitrous Oxide Inhalation Among Adolescents: Prevalence, Correlates, and Co-Occurrence with Volatile Solvent Inhalation

Few studies have examined the prevalence of nitrous oxide (NO) inhalation or co-occurrence of NO and volatile solvent (VS) use in adolescents. Study aims were to (1) describe the independent and conjoint prevalence of NO and VS use in incarcerated youth, (2) compare adolescent users of both NO and VS inhalants (NO+VS) to users of NO-only, VS-only, and nonusers of NO and VS (NO/VNS nonusers) with regard to demographic, psychological, and behavioral characteristics, and (3) conduct logistic regression analyses identifying correlates of NO use. Residents (N = 723) of Missouri Division of Youth Services were assessed with standardized psychosocial measures. Participants averaged 15.5 (SD = 1.2) years of age, were ethnically diverse and predominantly male. Lifetime prevalence of NO use was 15.8%. NO+VS users evidenced greater impairments compared to NO+VS nonusers. VS-only users evidenced impairments that were similar in kind but at lower prevalences compared to those displayed by NO+VS users, whereas NO-only youth had profiles that were similar to those of NO/VS nonusers. Psychiatric disorders, polydrug use, and temperamental fearlessness were correlates of NO use. NO+VS users were at high risk for behavioral and emotional problems. Screening and interventions for NO and VS inhalant use should be implemented in juvenile justice facilities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78160/1/nihms217666.pd

Effects of exercise timing on sleep architecture and nocturnal blood pressure in prehypertensives

Kimberly Fairbrother,1 Ben Cartner,1 Jessica R Alley,1 Chelsea D Curry,1, David L Dickinson,2 David M Morris,1 Scott R Collier1 1Vascular Biology and Autonomic Studies Laboratory, Department of Health and Exercise Science, 2Department of Economics, Appalachian State University, Boone, NC, USA Background: During nocturnal sleep, blood pressure (BP) “dips” compared to diurnal BP, reducing stress on the cardiovascular system. Both the hypotensive response elicited by acute aerobic exercise and sleep quality can impact this dipping response. Purpose: The purpose of this study was to investigate the effects of aerobic exercise timing on circadian BP changes and sleep architecture. Materials and methods: Twenty prehypertensive subjects completed the study. During four test sessions, participants first completed a graded exercise test to exhaustion and then performed 30 minutes of treadmill exercise at 7 am (7A), 1 pm (1P), and 7 pm (7P) in a random, counterbalanced order at 65% of the heart rate obtained at peak oxygen uptake. An ambulatory cuff was used to monitor BP responses during 24 hours following exercise, and an ambulatory sleep-monitoring headband was worn during sleep following each session. Results: Aerobic exercise at 7A invoked a greater dip in nocturnal systolic BP than exercise at 1P or 7P, although the greatest dip in nocturnal diastolic BP occurred following 7P. Compared to 1P, 7A also invoked greater time spent in deep sleep. Conclusion: These data indicate that early morning may be the most beneficial time to engage in aerobic exercise to enhance nocturnal BP changes and quality of sleep. Keywords: nocturnal dipping, prehypertension, aerobic exercis

Prior infection exacerbates postoperative cognitive dysfunction in aged rats

Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro)inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasma pulmonis, this presented the unique opportunity to investigate whether a pulmonary infection before surgery influences surgery-induced neuroinflammation and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma infection (infection) and control rats (healthy) were subjected to abdominal surgery and jugular vein catheterization under general anesthesia (surgery) or remained naïve (control). In postoperative week 2, behavioral tests were performed to assess cognitive performance and exploratory behavior. The acute systemic inflammatory response was investigated by measuring plasma IL-6 and IL-12. In the hippocampus, prefrontal cortex and striatum, microglial activity, neurogenesis, and concentrations of IL-6, IL-12, IL1B, and brain-derived neurotropic factor on postoperative day 14 were determined. Rats still showed signs of increased neuroinflammatory activity, as well as cognitive and behavioral changes, 3 wk after the symptoms of infection had subsided. Rats that had experienced infection before surgery exhibited a more generalized and exacerbated postoperative cognitive impairment compared with healthy surgery rats, as well as a prolonged increase in systemic cytokine levels and increased microglial activation in the hippocampus and prefrontal cortex. These findings support the hypothesis that an infection before surgery under general anesthesia exacerbates POCD. Future studies are necessary to determine whether the found effects are aging specific and to investigate the magnitude and time course of this effect in a controlled manner. © 2015 the American Physiological Society