55 research outputs found
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Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis
Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M (IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSFâdependent IgM, ensures effective early frontline defense against bacteria invading the lungs. The study describes a previously unrecognized GM-CSF-IgM axis and positions IRA B cells as orchestrators of protective IgM immunity
Lack of group X secreted phospholipase A<sub>2</sub> increases survival following pandemic H1N1 influenza infection
The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GXâ/â) model and found that survival after infection was significantly greater in GXâ/â mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GXâ/â mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GXâ/â mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza
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Local proliferation dominates lesional macrophage accumulation in atherosclerosis
During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall1,2. The observation that circulating monocytes give rise to lesional macrophages3â9 has reinforced the concept that monocyte infiltration dictates macrophage build-up. Recent work indicates, however, that macrophages do not depend on monocytes in some inflammatory contexts10. We therefore revisited the mechanism of macrophage accumulation in atherosclerosis. We show that murine atherosclerotic lesions experience a surprisingly rapid, 4-week, cell turnover. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation via the involvement of scavenger receptor (SR)-A. Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease
Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)[superscript +] macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE[superscript â/â] mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques
Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth
Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1+ precursors and postnatally from bone marrowâderived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche
The 13th Southern Hemisphere Conference on the Teaching and Learning of Undergraduate Mathematics and Statistics
NgÄ mihi aroha ki ngÄ tangata katoa and warm greetings to you all. Welcome to Herenga
Delta 2021, the Thirteenth Southern Hemisphere Conference on the Teaching and Learning
of Undergraduate Mathematics and Statistics.
It has been ten years since the Volcanic Delta Conference in Rotorua, and we are excited to
have the Delta community return to Aotearoa New Zealand, if not in person, then by virtual
means. Although the limits imposed by the pandemic mean that most of this yearâs 2021
participants are unable to set foot in TÄmaki Makaurau Auckland, this has certainly not
stopped interest in this event. Participants have been invited to draw on the concept of
herenga, in Te Reo MÄori usually a mooring place where people from afar come to share
their knowledge and experiences. Although many of the participants are still some distance
away, the submissions that have been sent in will continue to stimulate discussion on
mathematics and statistics undergraduate education in the Delta tradition.
The conference invited papers, abstracts and posters, working within the initial themes of
Values and Variables. The range of submissions is diverse, and will provide participants with
many opportunities to engage, discuss, and network with colleagues across the Delta
community. The publications for this thirteenth Delta Conference include publications in the
International Journal of Mathematical Education in Science and Technology, iJMEST,
(available at https://www.tandfonline.com/journals/tmes20/collections/Herenga-Delta-2021),
the Conference Proceedings, and the Programme (which has created some interesting
challenges around time-zones), by the Local Organizing Committee. Papers in the iJMEST
issue and the Proceedings were peer reviewed by at least two reviewers per paper. Of the
ten submissions to the Proceedings, three were accepted.
We are pleased to now be at the business end of the conference and hope that this event will
carry on the special atmosphere of the many Deltas which have preceded this one. We hope
that you will enjoy this conference, the virtual and social experiences that accompany it, and
take the opportunity to contribute to further enhancing mathematics and statistics
undergraduate education.
NgÄ manaakitanga,
Phil Kane (The University of Auckland | Waipapa Taumata Rau) on behalf of the Local
Organising Committ
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