Porphyromonas gingivalis gingipains cause defective macrophage migration towards apoptotic cells and inhibit phagocytosis of primary apoptotic neutrophils:gingipains, apoptotic cell removal & inflammation

Periodontal disease is a prevalent chronic inflammatory condition characterised by an aberrant host response to a pathogenic plaque biofilm resulting in local tissue damage and frustrated healing that can result in tooth loss. Cysteine proteases (gingipains) from the key periodontal pathogen Porphyromonas gingivalis have been implicated in periodontal disease pathogenesis by inhibiting inflammation resolution and are linked with systemic chronic inflammatory conditions such as rheumatoid arthritis. Efficient clearance of apoptotic cells is essential for the resolution of inflammation and tissue restoration. Here we sought to characterise the innate immune clearance of apoptotic cells and its modulation by gingipains. We examined the capacity of gingipain-treated macrophages to migrate towards and phagocytose apoptotic cells. Lysine gingipain treatment of macrophages impaired macrophage migration towards apoptotic neutrophils. Furthermore, lysine gingipain treatment reduced surface expression levels of CD14, a key macrophage receptor for apoptotic cells, which resulted in reduced macrophage interactions with apoptotic cells. Additionally, whilst apoptotic cells and their derived secretome were shown to inhibit TNF-α induced expression by P.gingivalis LPS, we demonstrated that gingipain preparations induced a rapid inflammatory response in macrophages that was resistant to the anti-inflammatory effects of apoptotic cells or their secretome. Taken together these data indicate that P.gingivalis may promote the chronic inflammation seen in periodontal disease patients by multiple mechanisms including rapid, potent gingipain-mediated inflammation coupled with receptor cleavage leading to defective clearance of apoptotic cells and reduced anti-inflammatory responses. Thus gingipains represent a potential therapeutic target for intervention in the management of chronic periodontal disease

Smoking patterns and stimulus control in intermittent and daily smokers

Intermittent smokers (ITS) - who smoke less than daily - comprise an increasing proportion of adult smokers. Their smoking patterns challenge theoretical models of smoking motivation, which emphasize regular and frequent smoking to maintain nicotine levels and avoid withdrawal, but yet have gone largely unexamined. We characterized smoking patterns among 212 ITS (smoking 4-27 days per month) compared to 194 daily smokers (DS; smoking 5-30 cigarettes daily) who monitored situational antecedents of smoking using ecological momentary assessment. Subjects recorded each cigarette on an electronic diary, and situational variables were assessed in a random subset (n = 21,539 smoking episodes); parallel assessments were obtained by beeping subjects at random when they were not smoking (n = 26,930 non-smoking occasions). Compared to DS, ITS' smoking was more strongly associated with being away from home, being in a bar, drinking alcohol, socializing, being with friends and acquaintances, and when others were smoking. Mood had only modest effects in either group. DS' and ITS' smoking were substantially and equally suppressed by smoking restrictions, although ITS more often cited self-imposed restrictions. ITS' smoking was consistently more associated with environmental cues and contexts, especially those associated with positive or "indulgent" smoking situations. Stimulus control may be an important influence in maintaining smoking and making quitting difficult among ITS. © 2014 Shiffman et al

Sequencing of diverse mandarin, pummelo and orange genomes reveals complex history of admixture during citrus domestication

Cultivated citrus are selections from, or hybrids of, wild progenitor species whose identities and contributions to citrus domestication remain controversial. Here we sequence and compare citrus genomes-a high-quality reference haploid clementine genome and mandarin, pummelo, sweet-orange and sour-orange genomes-and show that cultivated types derive from two progenitor species. Although cultivated pummelos represent selections from one progenitor species, Citrus maxima, cultivated mandarins are introgressions of C. maxima into the ancestral mandarin species Citrus reticulata. The most widely cultivated citrus, sweet orange, is the offspring of previously admixed individuals, but sour orange is an F1 hybrid of pure C. maxima and C. reticulata parents, thus implying that wild mandarins were part of the early breeding germplasm. A Chinese wild 'mandarin' diverges substantially from C. reticulata, thus suggesting the possibility of other unrecognized wild citrus species. Understanding citrus phylogeny through genome analysis clarifies taxonomic relationships and facilitates sequence-directed genetic improvement. (Résumé d'auteur

Key mechanisms governing resolution of lung inflammation

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered