Sec22b Regulates Inflammatory Responses by Controlling the Nuclear Translocation of NF-κB and the Secretion of Inflammatory Mediators.

Soluble -ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) regulate the vesicle transport machinery in phagocytic cells. Within the secretory pathway, Sec22b is an endoplasmic reticulum-Golgi intermediate compartment (ERGIC)-resident SNARE that controls phagosome maturation and function in macrophages and dendritic cells. The secretory pathway controls the release of cytokines and may also impact the secretion of NO, which is synthesized by the Golgi-active inducible NO synthase (iNOS).

Leishmania donovani Metacyclic Promastigotes Impair Phagosome Properties in Inflammatory Monocytes.

Leishmaniasis, a debilitating disease with clinical manifestations ranging from self-healing ulcers to life-threatening visceral pathologies, is caused by protozoan parasites of the genus. These professional vacuolar pathogens are transmitted by infected sand flies to mammalian hosts as metacyclic promastigotes and are rapidly internalized by various phagocyte populations. Classical monocytes are among the first myeloid cells to migrate to infection sites.

Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts.

The protozoan parasite Leishmania donovani (L. donovani) causes visceral leishmaniasis, a chronic infection which is fatal when untreated. Herein, we investigated whether in addition to altering transcription, L.

: Strain-Specific Modulation of Phagosome Maturation.

() is responsible for the largest number of American tegumentary leishmaniasis (ATL) in Brazil. ATL can present several clinical forms including typical (TL) and atypical (AL) cutaneous and mucocutaneous (ML) lesions. To identify parasite and host factors potentially associated with these diverse clinical manifestations, we first surveyed the expression of two virulence-associated glycoconjugates, lipophosphoglycan (LPG) and the metalloprotease GP63 by a panel of promastigotes of Leishmania braziliensis strains isolated from patients with different clinical manifestations of ATL and from the sand fly vector.

The host cell secretory pathway mediates the export of Leishmania virulence factors out of the parasitophorous vacuole.

To colonize phagocytes, Leishmania subverts microbicidal processes through components of its surface coat that include lipophosphoglycan and the GP63 metalloprotease. How these virulence glycoconjugates are shed, exit the parasitophorous vacuole (PV), and traffic within host cells is poorly understood. Here, we show that lipophosphoglycan and GP63 are released from the parasite surface following phagocytosis and redistribute to the endoplasmic reticulum (ER) of macrophages.

Lipophosphoglycan-Deficient Mutants: A Tool to Study Host Cell-Parasite Interplay.

Lipophosphoglycan (LPG) is the major surface glycoconjugate of metacyclic promastigotes and is associated with virulence in various species of this parasite. Here, we generated a LPG-deficient mutant of , the foremost etiologic agent of visceral leishmaniasis in Brazil. The LPG-deficient mutant (Δ) was obtained by homologous recombination and complemented via episomal expression of (Δ + ).

Understanding TGEV-ETEC Coinfection through the Lens of Proteomics: A Tale of Porcine Diarrhea.

Porcine diarrhea and gastroenteritis are major causes of piglet mortality that result in devastating economic losses to the industry. A plethora of pathogens can cause these diseases, with the transmissible gastroenteritis virus (TGEV) and enterotoxigenic Escherichia coli K88 (ETEC) being two of the most salient. In the December 2017 issue of Proteomics Clinical Aplications, Xia and colleagues used comparative proteomics to shed light on how these microbes interact to cause severe disease .

Macrophages Tell the Non-Professionals What to Do.

Phagocytosis by professional and non-professional phagocytes plays a critical role in tissue homeostasis and the immune response. Using an airway inflammation model, Han et al. (2016) report in Nature that macrophages secrete IGF-1 to signal epithelial cells to stop ingesting apoptotic cells while increasing the uptake of anti-inflammatory macrophage-derived microvesicles.

Leishmania survival in the macrophage: where the ends justify the means.

Macrophages are cells of the immune system that mediate processes ranging from phagocytosis to tissue homeostasis. Leishmania has evolved ingenious ways to adapt to life in the macrophage. The GP63 metalloprotease, which disables key microbicidal pathways, has recently been found to disrupt processes ranging from antigen cross-presentation to nuclear pore dynamics.

Macrophage cytokines: involvement in immunity and infectious diseases.

The evolution of macrophages has made them primordial for both development and immunity. Their functions range from the shaping of body plans to the ingestion and elimination of apoptotic cells and pathogens. Cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells.

Leishmania promastigotes induce cytokine secretion in macrophages through the degradation of synaptotagmin XI.

Synaptotagmins (Syts) are type-I membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis. We recently discovered that Syt XI is a recycling endosome- and lysosome-associated protein that negatively regulates the secretion of TNF and IL-6. In this study, we show that Syt XI is directly degraded by the zinc metalloprotease GP63 and excluded from Leishmania parasitophorous vacuoles by the promastigotes surface glycolipid lipophosphoglycan.

Leishmania dices away cholesterol for survival.

Host lipid alterations are centrally involved in Leishmania donovani infection, and infected patients exhibit hypocholesterolemia. In this issue of Cell Host & Microbe, Ghosh et al. (2013) show that the metalloprotease GP63 released by L.

Synaptotagmin XI regulates phagocytosis and cytokine secretion in macrophages.

Synaptotagmins (Syts) are a group of type I membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis. All Syts possess a single transmembrane domain, and two conserved tandem Ca(2+)-binding C2 domains. However, Syts IV and XI possess a conserved serine in their C2A domain that precludes these Syts from binding Ca(2+) and phospholipids, and from mediating vesicle fusion.