Article

Lung Infection—A Public Health Priority

Harvard School of Public Health, Boston, Massachusetts, USA.
PLoS Medicine (Impact Factor: 14.43). 03/2006; 3(2):e76. DOI: 10.1371/journal.pmed.0030076
Source: PubMed

ABSTRACT

The pervasive burden of lung infections receives proportionately little attention from the biomedical and public health communities, argues Mizgerd.

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    • "Pneumonia, an acute respiratory tract bacterial infection is a major cause of deaths around the globe (Mizgerd, 2006) making 35% of the mortalities caused by infectious diseases (WHO). Critically ill patients present severe sepsis that result in multiple organ failure leading to death (Russel, 2006). "
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    ABSTRACT: The emerging role of the TREMs (Triggering Receptors Expressed by Myeloid cells) family in inflammation makes it important to explore their molecular mechanisms governing key pathways in inflammatory diseases. The TREMs family interaction with microbial products make it a strong candidate to target inflammatory diseases and raises an important question of its potential as a useful target in inflammatory diseases caused by products other than microbes, for example psoriasis. The interaction of TREMs with various immune responses can be of key importance in handling inflammatory diseases. The well established interaction of TREM-1 with microbial products like LPS and the emerging interactions with products from different important diseases of brain, heart, lungs and skin demands its full investigation as a therapeutic target. The post translational modifications (PTMs) that might regulate the functions of genes are also discussed and its future potential is reviewed. Furthermore, Its close cross talk with TLRs, NLRs and NODs is also reviewed in context of developing novel therapeutics.
    Full-text · Article · Jan 2016 · Current issues in molecular biology
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    • "Infectious pneumonias are a leading cause of worldwide morbidity and mortality, with a greater annual burden of disease than HIV, malaria, and tuberculosis (Mizgerd, 2006). The bacterium Yersinia pestis is an infamous example of an easily transmitted pathogen that causes respiratory infections. "
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    ABSTRACT: Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis. The bacterial protease Pla contributes to disease progression and manipulation of host immunity, but the mechanisms by which this occurs are largely unknown. Here we show that Pla degrades the apoptotic signaling molecule Fas ligand (FasL) to prevent host cell apoptosis and inflammation. Wild-type Y. pestis, but not a Pla mutant (Δpla), degrades FasL, which results in decreased downstream caspase-3/7 activation and reduced apoptosis. Similarly, lungs of mice challenged with wild-type Y. pestis show reduced levels of FasL and activated caspase-3/7 compared to Δpla infection. Consistent with a role for FasL in regulating immune responses, Δpla infection results in aberrant proinflammatory cytokine levels. The loss of FasL or inhibition of caspase activity alters host inflammatory responses and enables enhanced Y. pestis outgrowth in the lungs. Thus, by degrading FasL, Y. pestis manipulates host cell death pathways to facilitate infection.
    Full-text · Article · Apr 2014 · Cell host & microbe
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    • "The World Health Organization (WHO) estimates that lower respiratory tract infections account for nearly 35% of all deaths from infectious diseases, causing an annual mortality of nearly 4 million adults and children. Thus, bacterial pneumonia is a significant cause of mortality worldwide 1. "
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    ABSTRACT: Objective: In the acute stage of infectious diseases such as pneumonia and sepsis, sequelae hypercytokinemia and cytokine storm are often observed simultaneously. During bacterial infections, activated polymorphonuclear leukocytes (PMNs) cause inflammation and organ dysfunction in severely ill patients. Gene expression of the triggering receptor on myeloid cells (TREM)-1 and G-coupled-protein receptor kinase (GRK)-2 in PMNs isolated from patients was analysed to identify genes correlated with the severity of pathophysiological conditions. Methods: mRNA levels of TREM1 and GRK2 in the PMNs from 26 patients (13 with pneumonia, 5 with severe sepsis, and 8 with septic shock) were analysed by using quantitative real-time PCR. The synthesised soluble form (s)TREM-1 was incubated with normal PMNs to investigate its biological functions in vitro. Results: Copies of TREM1 transcript were 0.7- to 2.1-fold higher in patients with pneumonia compared to those of normal subjects; the average fold-change was 1.1-fold. The mRNA levels of patients suffering from severe sepsis and septic shock were 0.34- and 0.33-fold lower compared to those of healthy subjects, respectively. TREM1 mRNA levels in 5 of 26 patients in convalescent stages recovered to normal levels. The mRNA levels of GRK2 in the PMNs of patients were also downregulated. The synthesised sTREM-1 upregulated the mRNA levels of TREM1 in normal PMNs. Conclusions: TREM1 mRNA levels were inversely correlated with the severity of pathophysiological conditions in acute bacterial infections. The gene expression levels of TREM1 in PMNs isolated from patients with bacterial infections may be used as a surrogate biomarker for determining the severity.
    Preview · Article · Jan 2014 · International journal of medical sciences
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