Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils

Corleis, Björn; Korbel, Daniel S.; Wilson, Roland; Bylund, Johan; Chee, Ronnie; Schaible, Ulrich E.

doi:10.1111/j.1462-5822.2012.01783.x

Cited by 121 publications

(130 citation statements)

References 53 publications

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“…In patients with cultureconfirmed TBM, AFB was predominantly seen within neutrophils, whereas in those with culture-negative disease the bacteria were mostly found within monocytes (see Figure E2). Recent data suggest that human neutrophils are relatively poor killers of M. tuberculosis compared with monocytes and macrophages (16), which may explain why AFB contained predominantly within monocytes failed to grow. There is a complex and poorly understood relationship between the numbers and types of leukocytes in the CSF, the bacterial load, and clinical outcome from TBM.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Intracellular Mycobacterium tuberculosis Detection for Tuberculous Meningitis

Feng¹,

Shi²,

Lei³

et al. 2014

Am J Respir Crit Care Med

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Rationale: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity.Objectives: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis.Methods: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis.Measurements and Main Results: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled.Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively.Conclusions: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Intracellular Mycobacterium tuberculosis Detection for Tuberculous Meningitis

Feng¹,

Shi²,

Lei³

et al. 2014

Am J Respir Crit Care Med

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“…Investigations on propensities of PMNs to eradicate M. tuberculosis generated conflicting results (11). Some reported mycobactericidal activities of human PMNs (12)(13)(14)(15), while others demonstrated that human PMNs phagocytose M. tuberculosis but fail to kill the bacilli (16)(17)(18)(19)(20). In the zebrafish model of mycobacterial infection, PMNs kill Mycobacterium marinum through phagocytosis of infected macrophages and thereby contribute to host defense (21).…”

Section: Introductionmentioning

confidence: 99%

CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis

Nouailles¹,

Dorhoi²,

Koch³

et al. 2014

J. Clin. Invest.

190

185

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Successful host defense against numerous pulmonary infections depends on bacterial clearance by polymorphonuclear leukocytes (PMNs); however, excessive PMN accumulation can result in life-threatening lung injury. Local expression of CXC chemokines is critical for PMN recruitment. The impact of chemokinedependent PMN recruitment during pulmonary Mycobacterium tuberculosis infection is not fully understood. Here, we analyzed expression of genes encoding CXC chemokines in M. tuberculosis-infected murine lung tissue and found that M. tuberculosis infection promotes upregulation of Cxcr2 and its ligand Cxcl5. To determine the contribution of CXCL5 in pulmonary PMN recruitment, we generated Cxcl5 -/-mice and analyzed their immune response against M. tuberculosis. Both Cxcr2 -/-mice and Cxcl5 -/-mice, which are deficient for only one of numerous CXCR2 ligands, exhibited enhanced survival compared with that of WT mice following high-dose M. tuberculosis infection. The resistance of Cxcl5 -/-mice to M. tuberculosis infection was not due to heightened M. tuberculosis clearance but was the result of impaired PMN recruitment, which reduced pulmonary inflammation. Lung epithelial cells were the main source of CXCL5 upon M. tuberculosis infection, and secretion of CXCL5 was reduced by blocking TLR2 signaling. Together, our data indicate that TLR2-induced epithelial-derived CXCL5 is critical for PMN-driven destructive inflammation in pulmonary tuberculosis.

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“…Although macrophages play a vital role in controlling and eliminating the intracellular pathogen, large numbers of neutrophils are recruited to the lungs in the initial stages of an Mtb infection [8,9]. Neutrophils are not able to kill virulent Mtb [10]; however, neutrophil recruitment appears to be important for early granuloma formation and containment of the infection [11]. A crosstalk between neutrophils and other immune cells has been described [12], where the release of granule proteins attracts other immune cells and also modulates the function of tissue-resident cells.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis-Induced Neutrophil Extracellular Traps Activate Human Macrophages

Braian

Hogea

Stendahl³

2013

J Innate Immun

130

159

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Neutrophils activated by Mycobacterium tuberculosis (Mtb) form neutrophil extracellular traps (NETs), containing DNA and several biologically active cytosolic and granular proteins. These NETs may assist in the innate immune defense against different pathogens. We investigated whether the NET-forming neutrophils mediate an activating signal to macrophages during the early multicellular inflammatory reaction and granuloma formation. Mtb-induced NETs were found to be reactive oxygen species dependent and phagocytosis dependent. A neutrophil elastase inhibitor also delayed NET formation. However, NET formation occurred independently of Mtb-induced apoptosis. We observed close interactions between macrophages and Mtb-activated neutrophils, where macrophages bound and phagocytosed NETs. Significant secretion of the cytokines interleukin (IL)-6, tumor necrosis factor-α, IL-1β and IL-10 were detected from macrophages cocultured with NETs from Mtb-activated but not phorbol myristate acetate-activated neutrophils. NETs binding heat shock protein 72 (Hsp72) or recombinant Hsp72 were able to trigger cytokine release from macrophages. Only Mtb-induced NETs contained Hsp72, suggesting that these NETs can transfer this danger signal to adjacent macrophages. We propose that Hsp72 sequestered in NETs plays an important role in the interaction between neutrophils and macrophages during the early innate immune phase of an Mtb infection. The immunomodulatory role of NETs and proteins derived from them may influence not only chronic inflammation during tuberculosis but also immune regulation and autoimmunity.

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Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils

Cited by 121 publications

References 53 publications

Diagnostic Accuracy of Intracellular Mycobacterium tuberculosis Detection for Tuberculous Meningitis

Diagnostic Accuracy of Intracellular Mycobacterium tuberculosis Detection for Tuberculous Meningitis

CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis

Mycobacterium tuberculosis-Induced Neutrophil Extracellular Traps Activate Human Macrophages

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