Mycobacterium smegmatis Bacteria Expressing Mycobacterium tuberculosis-Specific Rv1954A Induce Macrophage Activation and Modulate the Immune Response

Mycobacterium tuberculosis (M. tb), the intracellular pathogen causing tuberculosis, has developed mechanisms that endow infectivity and allow it to modulate host immune response for its survival. Genomic and proteomic analyses of non-pathogenic and pathogenic mycobacteria showed presence of genes and proteins that are specific to M. tb. In silico studies predicted that M.tb Rv1954A is a hypothetical secretory protein that exhibits intrinsically disordered regions and possess B cell/T cell epitopes. Treatment of macrophages with Rv1954A led to TLR4-mediated activation with concomitant increase in secretion of pro-inflammatory cytokines, IL-12 and TNF-α. In vitro studies showed that rRv1954A protein or Rv1954A knock-in M. smegmatis (Ms_Rv1954A) activates macrophages by enhancing the expression of CD80 and CD86. An upregulation in the expression of CD40 and MHC I/II was noted in the presence of Rv1954A, pointing to its role in enhancing the association of APCs with T cells and in the modulation of antigen presentation, respectively. Ms_Rv1954A showed increased infectivity, induction of ROS and RNS, and apoptosis in RAW264.7 macrophage cells. Rv1954A imparted protection against oxidative and nitrosative stress, thereby enhancing the survival of Ms_Rv1954A inside macrophages. Mice immunized with Ms_Rv1954A showed that splenomegaly and primed splenocytes restimulated with Rv1954A elicited a Th1 response. Infection of Ms_Rv1954A in mice through intratracheal instillation lead...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research

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Yohei Sasakawa – WHO Goodwill Ambassador for Leprosy Elimination and Chairman of Sasakawa Health Foundation speaking at the 3rd of the “Don’t Forget Leprosy” webinar series organized by Sasakawa Health Foundation on Dec 2. Credit: Stella PaulBy Stella PaulHyderabad, Dec 3 2021 (IPS) As 2021 nears its end, public health systems worldwide remain severely strained by COVID 19, which is showing no sign of ending. But even as countries battle to control the deadly pandemic, they must also maintain the progress made against other diseases, including leprosy, global leprosy experts and advocates have urged...
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SPRING HOUSE, PENNSYLVANIA, December 3, 2021 – The Janssen Pharmaceutical Companies of Johnson &Johnson today announced new TREMFYA® (guselkumab) efficacy and safety data from the Phase 3b COSMOS trial published in Annals of the Rheumatic Diseases (ARD), evaluating this selective interleukin (IL)-23 inhibitor in adults with active psoriatic arthritis (PsA) who demonstrated inadequate efficacy or intolerance to tumor necrosis factor inhibition (TNFi).1 Results showed significantly higher proportions of patients treated with TREMFYA had improvement in joint signs and symptoms and complete skin clearance versus ...
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Source: Human Vaccines and Immunotherapeutics - Category: Allergy & Immunology Authors: Source Type: research
The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, was downregulated in macrophages after Mycobacterial infection. Inhibition of SIRT7 with the pan-sirtuin family inhibitor nicotinamide (NAM), or by silencing SIRT7 expression, promoted intracellular growth of Mtb and restricted the generation of nitric oxide (NO)...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Approximately one-fourth of the global population is latently infected with Mycobacterium tuberculosis. An understanding of the burden of latent tuberculosis infection (LTBI) among immigrants compared with the ge...
Source: BMC Infectious Diseases - Category: Infectious Diseases Authors: Tags: Research Source Type: research
Lipid droplets (LDs) are commonly found in various biological cells and are organelles related to cell metabolism. LDs, the number and size of which are heterogeneous across cell type, are primarily composed of polar lipids and proteins on the surface with neutral lipids in the core. Neutral lipids stored in LDs can be degraded by lipolysis and lipophagocytosis, which are regulated by various proteins. The process of LD formation can be summarized in four steps. In addition to energy production, LDs play an extremely pivotal role in a variety of physiological and pathological processes, such as endoplasmic reticulum stress...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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Source: Journal of Inflammation Research - Category: Allergy & Immunology Tags: Journal of Inflammation Research Source Type: research
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Source: South African Medical Journal - Category: African Health Authors: Source Type: research
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Source: South African Medical Journal - Category: African Health Authors: Source Type: research
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