A Bumpy Ride of Mycobacterial Phagosome Maturation: Roleplay of Coronin1 Through Cofilin1 and cAMP

Phagosome-lysosome fusion in innate immune cells like macrophages and neutrophils marshal an essential role in eliminating intracellular microorganisms. In microbe-challenged macrophages, phagosome-lysosome fusion occurs 4 to 6 h after the phagocytic uptake of the microbe. However, live pathogenic mycobacteria hinder the transfer of phagosomes to lysosomes, up to 20 h post-phagocytic uptake. This period is required to evade pro-inflammatory response and upregulate the acid-stress tolerant proteins. The exact sequence of events through which mycobacteria retards phagolysosome formation remains an enigma. The macrophage coat protein Coronin1(Cor1) is recruited and retained by mycobacteria on the phagosome membrane to retard its maturation by hindering the access of phagosome maturation factors. Mycobacteria-infected macrophages exhibit an increased cAMP level, and based on receptor stimulus, Cor1 expressing cells show a higher level of cAMP than non-Cor1 expressing cells. Here we have shown that infection of bone marrow-derived macrophages with H37Rv causes a Cor1 dependent rise of intracellular cAMP levels at the vicinity of the phagosomes. This increased cAMP fuels cytoskeletal protein Cofilin1 to depolymerize F-actin around the mycobacteria-containing phagosome. Owing to reduced F-actin levels, the movement of the phagosome toward the lysosomes is hindered, thus contributing to the retarded phagosome maturation process. Additionally, Cor1 mediated upregulation of C...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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ConclusionsDespite a good antiretroviral coverage, HIV infection is still diagnosed late in our country. The emphasis must be on the promotion of voluntary testing mainly among groups at high risk of infection.Key messagesMore active offer of HIV testing, by general practitioners, should play a crucial role in the early identification of HIV infections.Strategies such as use of preexposure prophylaxis should be developed to prevent HIV transmission among MSM.
Source: The European Journal of Public Health - Category: General Medicine Source Type: research
Non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in immune cells development and function. Their expression is altered in different physiological and disease conditions, hence making them attractive targets for the understanding of disease etiology and the development of adjunctive control strategies, especially within the current context of mitigated success of control measures deployed to eradicate these diseases. In this review, we summarize our current understanding of the role of ncRNAs in the etiology and control of major human tr...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Am J Trop Med Hyg. 2021 Oct 18:tpmd210133. doi: 10.4269/ajtmh.21-0133. Online ahead of print.ABSTRACTTuberculosis (TB) remains the leading cause of hospitalization and in-hospital mortality in HIV-positive adults. Using data from hospital and clinic files, research databases, and autopsy, we describe causes and outcomes of admissions, and assess investigations for TB among adults with advanced HIV who were hospitalized after enrollment into the TB Fast Track trial in South Africa (2013-2015). A total of 251 adults [median CD4 count, 37.5 cells/μL; interquartile range, 14-68 cells/µL; 152 (60.6%) on antiretroviral ...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Source Type: research
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Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Perspective Source Type: research
[African Union] The African continent is making headway in the fight against malaria among young children. Being at the forefront in establishing, strengthening, and supporting member states in disease control and surveillance for priority diseases including HIV and AIDs, tuberculosis, malaria, COIVD-19, hepatitis, and non-communicable diseases in the region, the African Union (AU) through the Africa Centres for Disease Control and Prevention (Africa CDC) has welcomed the World Health Organization's (WHO) historic go-ahea
Source: AllAfrica News: Malaria - Category: Infectious Diseases Source Type: news
Am J Trop Med Hyg. 2021 Oct 11:tpmd210899. doi: 10.4269/ajtmh.21-0899. Online ahead of print.ABSTRACTCOVID-19 has had considerable global impact; however, in sub-Saharan Africa, it is one of several infectious disease priorities. Prioritization is normally guided by disease burden, but the highly age-dependent nature of COVID-19 and that of other infectious diseases make comparisons challenging unless considered through metrics that incorporate life-years lost and time lived with adverse health. Therefore, we compared the 2020 mortality and disability-adjusted life-years (DALYs) lost estimates for malaria, tuberculosis, an...
Source: Am J Trop Med Hyg - Category: Infectious Diseases Authors: Source Type: research
On Oct. 6, the World Health Organization recommended use of the first vaccine to fight malaria. The decision is momentous and highly anticipated for many reasons: among them is that this is the first vaccine to help reduce the risk of deadly severe malaria in young children in Sub-Saharan Africa, where the disease remains a leading killer. The vaccine offers hope that there can be a circle of learning from one pandemic to the next. Malaria, our oldest pandemic, may offer insights on how we can survive contemporary scourges like COVID-19. Malaria evolved at least 2.5 million years ago and first infected humans in rural part...
Source: TIME: Science - Category: Science Authors: Tags: Uncategorized health healthscienceclimate Source Type: news
Conditions:   HIV Coinfection;   Aids/Hiv Problem;   Tuberculosis, Pulmonary;   Human Immunodeficiency Virus;   Lentivirus Infections;   RNA Virus Infections Intervention:   Drug: Interferon-Gamma Sponsors:   SPP Pharmaclon Ltd.;   North-Western State Medical University named after I.I.Mechnikov Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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