Safari, S. | bioRxiv Science

bioRxiv2019

Salivary gland macrophages assist tissue-resident CD8+ T cell immune surveillance

Tissue macrophages and tissue resident memory CD8+ T cells (TRM) play important roles for pathogen sensing and rapid protection of barrier tissues. To date, it is incompletely understood how these two cell types cooperate for efficient organ surveillance during homeostasis. Here, we used intravital imaging to show that TRM dynamically crawled along tissue macrophages in murine submandibular salivary glands (SMG) during the memory phase following a viral infection. Ex vivo confined SMG TRM integrated an unexpectedly wide range of migration modes: in addition to chemokine-and adhesion receptor-driven motility, SMG TRM displayed a remarkable capacity of autonomous motility in the absence of chemoattractants and adhesive ligands. This unique intrinsic SMG TRM motility was transmitted by friction and adaptation to microenvironmental topography through protrusion insertion into permissive gaps. Analysis of extracellular space in SMG using super-resolution shadow imaging showed discontinuous attachment of tissue macrophages to neighboring epithelial cells, offering paths of least resistance for patrolling TRM. Upon tissue macrophage depletion, intraepithelial SMG TRM showed decreased motility and reduced epithelial crossing events, and failed to cluster in response to local inflammatory chemokine stimuli. In sum, our data uncover a continuum of SMG TRM migration modes and identify a new accessory function of tissue macrophages to facilitate TRM patrolling of the complex exocrine gland architecture.\n\nOne sentence summaryCombined in vitro and in vivo imaging of salivary gland-resident tissue memory CD8+ T cells (TRM) uncovers their unique migratory behavior and describes a novel accessory function of tissue macrophages to assist TRM surveillance.

immunology↗

bioRxiv2018

The impact of 10-valent Pneumococcal Conjugate Vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children.

BackgroundPneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes but the burden of pneumococcal disease in developing countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the impact of PCV on pneumonia incidence.\n\nMethodsWe linked prospective hospital surveillance for clinically-defined WHO severe or very-severe pneumonia at Kilifi County Hospital from 2002-2015 to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45,000 children aged <5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January 2011. In Kilifi, there was a catch-up campaign for children aged <5 years. We estimated the impact of PCV10 on pneumonia incidence through interrupted time series analysis accounting for seasonal and temporal trends.\n\nFindingsThe incidence of admission with clinically-defined pneumonia in 2002/3 was 21{middle dot}7/1000/year in children aged 2-59 months. This declined progressively over 13 years. By the end of March 2011, 61{middle dot}1% of children aged 2-11 months received [≥]2 doses and 62{middle dot}3% of children aged 12-59 months received [≥]1 dose of PCV10. Adjusted incidence rate ratios for admissions with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated with PCV10 introduction, were 0{middle dot}52 (95% CI 0{middle dot}32-0{middle dot}86), 0{middle dot}73 (95% CI 0{middle dot}54-0{middle dot}97) and 0{middle dot}63, (95% CI 0{middle dot}31-1{middle dot}26), respectively. The annual incidence of clinically-defined pneumonia in December 2010 was 12{middle dot}2/1000; this was reduced by 3{middle dot}3/1000 with PCV10 introduction.\n\nInterpretationOver 13 years, hospitalisations for clinically-defined pneumonia declined progressively at Kilifi County Hospital but fell abruptly by 27% in association with PCV10 introduction. The incidence of radiologically-confirmed pneumonia fell by 48%. The burden of childhood pneumonia in Kilifi, Kenya, has been reduced substantially by PCV10.\n\nFundingGavi, Wellcome Trust

epidemiology↗