scholarly journals Mosquito cellular immunity at single-cell resolution

Science ◽  
2020 ◽  
Vol 369 (6507) ◽  
pp. 1128-1132 ◽  
Author(s):  
Gianmarco Raddi ◽  
Ana Beatriz F. Barletta ◽  
Mirjana Efremova ◽  
Jose Luis Ramirez ◽  
Rafael Cantera ◽  
...  
Keyword(s):  
Single Cell ◽  
Transmembrane Protein ◽  
Human Pathogens ◽  
Protein Marker ◽  
Immune Priming ◽  
Cellular Events ◽  
Effector Genes ◽  
Evolutionarily Conserved ◽  
Factor Α ◽  
Necrosis Factor

Hemocytes limit the capacity of mosquitoes to transmit human pathogens. Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti mosquito vectors. Our data reveal the functional diversity of hemocytes, with different subtypes of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A previously unidentified cell type in An. gambiae, which we term “megacyte,” is defined by a specific transmembrane protein marker (TM7318) and high expression of lipopolysaccharide-induced tumor necrosis factor–α transcription factor 3 (LL3). Knockdown experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify and validate two main hemocyte lineages and find evidence of proliferating granulocyte populations. This atlas of medically relevant invertebrate immune cells at single-cell resolution identifies cellular events that underpin mosquito immunity to malaria infection.

scholarly journals Mosquito cellular immunity at single-cell resolution

2020 ◽  
Author(s):  
Gianmarco Raddi ◽  
Ana Beatriz F Barletta ◽  
Mirjana Efremova ◽  
Jose Luis Ramirez ◽  
Rafael Cantera ◽  
...  
Keyword(s):  
Single Cell ◽  
Transmembrane Protein ◽  
Blood Feeding ◽  
Human Pathogens ◽  
Protein Marker ◽  
Immune Priming ◽  
Cellular Events ◽  
Invertebrate Immunology ◽  
Immune Challenges ◽  
Rna In Situ Hybridization

AbstractInsect hemocytes are the functional equivalents of leukocytes and limit the capacity of mosquitoes to transmit human pathogens through phagocytosis, encapsulation, secretion of immune factors and immune priming (1, 2). Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti, two important mosquito vectors. Blood feeding, infection with malaria parasites and other immune challenges reveal a previously unknown functional diversity of hemocytes, with different types of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A new cell type, which we term megacyte, is defined in Anopheles by a unique transmembrane protein marker (TM7318) and high expression of LPS-Induced TNF-alpha transcription factor 3 (LL3). Knock-down experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify two main hemocyte lineages and find evidence of proliferating granulocyte populations. We validate our analysis with RNA in-situ hybridization and highlight the mobilization of sessile hemocytes into circulation upon infection. Our data (https://hemocytes.cellgeni.sanger.ac.uk/) provide the first atlas of medically relevant invertebrate immune cells at single cell resolution. It provides an important resource for invertebrate immunology by identifying cellular events that underpin mosquito immunity to malaria infection.

scholarly journals Autophagy Modulation in Lymphocytes From COVID-19 Patients: New Therapeutic Target in SARS-COV-2 Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Marta Vomero ◽  
Cristiana Barbati ◽  
Tania Colasanti ◽  
Alessandra Ida Celia ◽  
Mariangela Speziali ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Degradation Pathway ◽  
The Novel ◽  
Lysosomal Degradation ◽  
Tnf Α ◽  
Evolutionarily Conserved ◽  
Novel Coronavirus ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the “cytokine storm.” Among these, interleukin (IL)-6, tumor necrosis factor‐α (TNF‐α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF‐α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection.

Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated by tumour necrosis factor-α converting enzyme

2001 ◽  
Vol 357 (3) ◽  
pp. 787-794 ◽  
Author(s):  
Barbara E. SLACK ◽  
Leona K. MA ◽  
Ching Ching SEAH
Keyword(s):  
Amyloid Precursor Protein ◽  
Muscarinic Receptor ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transmembrane Protein ◽  
Precursor Protein ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

The amyloid precursor protein (APP) of Alzheimer's disease is a transmembrane protein that is cleaved within its extracellular domain, liberating a soluble N-terminal fragment (sAPPα). Putative mediators of this process include three members of the ADAM (a disintegrin and metalloprotease) family, ADAM9, ADAM10 and ADAM17/TACE (tumour necrosis factor-α converting enzyme). Tumour necrosis factor-α protease inhibitor (TAPI-1), an inhibitor of ADAMs, reduced constitutive and muscarinic receptor-stimulated sAPPα release in HEK-293 cells stably expressing M3 muscarinic receptors. However, the former was less sensitive to TAPI-1 (IC50 = 8.09μM) than the latter (IC50 = 3.61μM), suggesting that these processes may be mediated by different metalloproteases. Constitutive sAPPα release was increased several-fold in cells transiently transfected with TACE, and this increase was proportional to TACE expression. In contrast, muscarinic-receptor-activated sAPPα release was not altered in TACE transfectants. TACE-dependent constitutive release of co-transfected APP695 was inhibited by TAPI-1 with an IC50 of 0.92μM, a value significantly lower than the IC50s for inhibition of either constitutive or receptor-regulated sAPPα shedding mediated by endogenous secretases. The results indicate that TACE is capable of catalysing constitutive α-secretory cleavage of APP, but it is likely that additional members of the ADAM family mediate endogenous constitutive and receptor-coupled release of sAPPα in HEK-293cells.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

Sign in / Sign up

Export Citation Format

Share Document