Splenic Macrophage Subsets and Their Function during Blood-Borne Infections

Silva, Henrique Borges da; Fonseca, Raíssa; Pereira, Rosana M.; Cassado, Alexandra dos Anjos; Álvarez, José María; Lima, Maria Regina D’Império

doi:10.3389/fimmu.2015.00480

Cited by 160 publications

(145 citation statements)

References 75 publications

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“…Location of particles in the spleen appears diffuse on day 2 but the signal coalesces into discrete areas by day 5. This most likely represents a transfer of particle from the red pulp of the spleen into the marginal zones and white pulp, which are the primary locations of splenic macrophages [44]. …”

Section: Resultsmentioning

confidence: 99%

Bioimaging predictors of rilpivirine biodistribution and antiretroviral activities

et al. 2018

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Antiretroviral therapy (ART) has changed the outcome of human immunodeficiency virus type one (HIV-1) infection from certain death to a life free of disease co-morbidities. However, infected people must remain on life-long daily ART. ART reduces but fails to eliminate the viral reservoir. In order to improve upon current treatment regimens, our laboratory created long acting slow effective release (LASER) ART nanoformulated prodrugs from native medicines. LASER ART enables antiretroviral drugs (ARVs) to better reach target sites of HIV-1 infection while, at the same time, improve ART's half-life and potency. However, novel ARV design has been slowed by prolonged pharmacokinetic testing requirements. To such ends, tri-modal theranostic nanoparticles were created with single-photon emission computed tomography (SPECT/CT), magnetic resonance imaging (MRI) and fluorescence capabilities to predict LASER ART biodistribution. The created theranostic ARV probes were then employed to monitor drug tissue distribution and potency. Intrinsically Indium (In) radiolabeled, europium doped cobalt-ferrite particles and rilpivirine were encased in a polycaprolactone core surrounded by a lipid shell (InEuCF-RPV). Particle cell and tissue distribution, and antiretroviral activities were sustained in macrophage tissue depots. InEuCF-PCL/RPV particles injected into mice demonstrated co-registration of MRI and SPECT/CT tissue signals with RPV and cobalt. Cell and animal particle biodistribution paralleled ARV activities. We posit that particle selection can predict RPV distribution and potency facilitated by multifunctional theranostic nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Bioimaging predictors of rilpivirine biodistribution and antiretroviral activities

et al. 2018

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“…The spleen is essential to the rapid clearance of bloodborne pathogens (Borges da Silva et al, 2015). The splenic microarchitecture facilitates the filtering of the blood, with capture of foreign particles and antigen delivery.…”

Section: Resultsmentioning

confidence: 99%

“…5; (Todd et al, 2011)), suggesting that chemokine receptor signaling to tissue patterning can be dissociated from the cytoskeletal rearrangements required for cellular migration (Morley et al, 2010). The spleen functions to generate rapid immune response to bloodborne pathogens, such as Streptococcus pneumoniae (Borges da Silva et al, 2015). While splenic architecture appears to be normal, LPL −/− mice exhibited a delayed early IgM response to heat-killed pneumococcal antigen (Todd et al, 2011), suggesting functional impairment of either antigen delivery or lymphocyte activation.…”

Section: Discussionmentioning

confidence: 99%

L-Plastin promotes podosome longevity and supports macrophage motility

Zhou

Szasz

Stewart-Hutchinson

et al. 2016

Molecular Immunology

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Elucidating the molecular regulation of macrophage migration is essential for understanding the patho-physiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL−/− mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP+ mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL−/− mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility.

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“…5D). While red pulp macrophages mainly serve as scavengers of senescent erythrocytes, they may also play a role in the induction of innate and adaptive immunity [45]. We further detected an elevation in the levels of circulating peripheral blood proinflammatory monocytes in DCM compared to WT mice, but no difference in total blood monocytes.…”

Section: Discussionmentioning

confidence: 52%

Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation

Lynch

Ismahil

Jegga

et al. 2017

Journal of Molecular and Cellular Cardiology

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Cardiomyopathies are a leading cause of heart failure and are often caused by mutations in sarcomeric genes, resulting in contractile dysfunction and cellular damage. This may stimulate the production of a robust proinflammatory response. To determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (DCM) caused by MYBPC3 mutation, we used the well-characterized cMyBP-C(t/t) mouse model of DCM at 3 months of age. Compared to wild type (WT) mice, DCM mice exhibited significantly decreased fractional shortening (36.4±2% vs. 15.5±1.0%, p < 0.0001) and significantly increased spleen weight (5.3±0.3% vs. 7.2±0.4 mm/mg, p = 0.002). Intriguingly, flow cytometry analysis revealed a significant increase in total (CD45+CD11b+Ly6C−MHCII+F480+) macrophages (6.5±1.4% vs. 14.8±1.4%, p = 0.002) and classically activated (CD45+CD11b+Ly6C−MHCII+F480+CD206−) proinflammatory (M1) macrophages (3.4±0.8% vs. 10.3±1.2%, p = 0.0009) in DCM hearts as compared with WT hearts. These results were further confirmed by immunofluorescence analysis of heart tissue sections. Splenic red pulp (CD11b+Ly6C+MHCIIlowF480hi) macrophages were significantly elevated (2.4±0.1% vs. 1.3±0.1%, p = 0.0001) in DCM compared to WT animals. Serum cytokine analysis in DCM animals exhibited a significant increase (0.65±0.2 vs. 2.175±0.5 pg/mL, p = 0.02) in interleukin (IL)-6 compared to WT animals. Furthermore, RNAseq analysis revealed the upregulation of inflammatory pathways in the DCM hearts. Together, these data indicate a robust proinflammatory response in DCM hearts, likely in response to cellular damage triggered by MYBPC3 mutation and resultant contractile dysfunction.

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Splenic Macrophage Subsets and Their Function during Blood-Borne Infections

Cited by 160 publications

References 75 publications

Bioimaging predictors of rilpivirine biodistribution and antiretroviral activities

Bioimaging predictors of rilpivirine biodistribution and antiretroviral activities

L-Plastin promotes podosome longevity and supports macrophage motility

Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation

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