Expression and regulation of chemokines in mycobacterial infection

Méndez-Samperio, Patricia

doi:10.1016/j.jinf.2008.08.010

Cited by 44 publications

(41 citation statements)

References 115 publications

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“…The formation of granuloma is a move towards this goal, which is achieved by a coordinated recruitment of immune cells52. Chemokines like MCP1, RANTES, MIP1α and CXCL1 are known potent chemo-attractants for T-cells, monocytes; and neutrophils, respectively54. In addition to their canonical function, some chemokines like CXCL8 can also enhance bactericidal activity through non-oxidative mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2 expression to modulate host immune responses

Boro

Singh

Balaji

2016

Sci Rep

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Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20–like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner. Mtb-triggered Hippo signaling modulates the expression and secretion of chemokines (CXCL1 and CXCL2); as silencing MST1/2 compromised the ability of Mtb to furnish the same. Further insight into the mechanism of Hippo-mediated regulation of chemokines revealed the role for a non-canonical Hippo effector interferon (IFN) regulatory factor (IRF) 3 in the process and marked the effect to be independent of LATS1. Alongside their ability to guide directed recruitment of immune cells, we have uncovered a paracrine role for Hippo-mediated secretion of CXCL1 and CXCL2 in the production of anti-microbial peptides (beta-defensins), iNOS, NOX2 and pro-inflammatory molecules during mycobacterial infection of the host. This study highlights the involvement of TLR2-IRAK1/4-MST1/2-IRF3 axis in Mtb-triggered modulation of chemokines and identifies Hippo signaling as a novel regulator of host-mycobacterial interactions.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2 expression to modulate host immune responses

Boro

Singh

Balaji

2016

Sci Rep

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“…Less attention has been paid to chemokines which are considered to be derived from the innate arm and hence less specific. However, there has been increasing interest in chemokines as markers of infection and disease [21]. Among the chemokines, CXCL10/IP10, a chemokine induced by IFN- γ has shown promising results as marker of tuberculosis disease in children [22].…”

Section: Discussionmentioning

confidence: 99%

CCL2/MCP-I Genotype-Phenotype Relationship in Latent Tuberculosis Infection

et al. 2011

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Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition) with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in asymptomatic community controls with no known exposure to tuberculosis and in recently exposed household contacts of pulmonary tuberculosis patients. TST positivity was linked to higher concentrations of plasma CCL2 (Mann Whitney U test; p = 0.004) and was more marked when the G allele was present in TST+ asymptomatic controls (A/G; p = 0.01). Recent exposure also had a significant effect on CCL-2 levels and was linked to the G allele (p = 0.007). Therefore association studies for susceptibility or protection from disease should take into consideration the PPD status as well as recent exposure of the controls group used for comparison. Our results also suggest a role for CCL-2 in maintaining the integrity of granuloma in asymptomatic individuals with latent infection in high TB burden settings. Therefore additional studies into the role of CCL-2 in disease reactivation and progression are warranted.

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“…The characteristic granuloma formation found in mycobacterial infections is increasingly thought to be controlled by CC and CXC chemokines (124), and therefore understanding how (182). One study of the human Hsp70 protein has determined that is does bind to CD40.…”

Section: Bacterial Molecular Chaperones and Protein-folding Catalystsmentioning

confidence: 99%

Bacterial Virulence in the Moonlight: Multitasking Bacterial Moonlighting Proteins Are Virulence Determinants in Infectious Disease

2011

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2Men may not be able to multitask, but it is emerging that proteins can. This capacity of proteins to exhibit more than one function is termed protein moonlighting, and, surprisingly, many highly conserved proteins involved in metabolic regulation or the cell stress response have a range of additional biological actions which are involved in bacterial virulence. This review highlights the multiple roles exhibited by a range of bacterial proteins, such as glycolytic and other metabolic enzymes and molecular chaperones, and the role that such moonlighting activity plays in the virulence characteristics of a number of important human pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Helicobacter pylori, and Mycobacterium tuberculosis.

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Expression and regulation of chemokines in mycobacterial infection

Cited by 44 publications

References 115 publications

Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2 expression to modulate host immune responses

Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2 expression to modulate host immune responses

CCL2/MCP-I Genotype-Phenotype Relationship in Latent Tuberculosis Infection

Bacterial Virulence in the Moonlight: Multitasking Bacterial Moonlighting Proteins Are Virulence Determinants in Infectious Disease

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