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

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CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. / Nouailles, Geraldine; Dorhoi, Anca; Koch, Markus; Zerrahn, Jens; Weiner, January; Faé, Kellen C; Arrey, Frida; Kuhlmann, Stefanie; Bandermann, Silke; Loewe, Delia; Mollenkopf, Hans-Joachim; Vogelzang, Alexis; Meyer-Schwesinger, Catherine; Mittrücker, Hans-Willi; McEwen, Gayle; Kaufmann, Stefan H E.

In: J CLIN INVEST, Vol. 124, No. 3, 03.03.2014, p. 1268-82.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Nouailles, G, Dorhoi, A, Koch, M, Zerrahn, J, Weiner, J, Faé, KC, Arrey, F, Kuhlmann, S, Bandermann, S, Loewe, D, Mollenkopf, H-J, Vogelzang, A, Meyer-Schwesinger, C, Mittrücker, H-W, McEwen, G & Kaufmann, SHE 2014, 'CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis', J CLIN INVEST, vol. 124, no. 3, pp. 1268-82. https://doi.org/10.1172/JCI72030

APA

Nouailles, G., Dorhoi, A., Koch, M., Zerrahn, J., Weiner, J., Faé, K. C., Arrey, F., Kuhlmann, S., Bandermann, S., Loewe, D., Mollenkopf, H-J., Vogelzang, A., Meyer-Schwesinger, C., Mittrücker, H-W., McEwen, G., & Kaufmann, S. H. E. (2014). CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J CLIN INVEST, 124(3), 1268-82. https://doi.org/10.1172/JCI72030

Vancouver

Nouailles G, Dorhoi A, Koch M, Zerrahn J, Weiner J, Faé KC et al. CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J CLIN INVEST. 2014 Mar 3;124(3):1268-82. https://doi.org/10.1172/JCI72030

Bibtex

@article{204fbe0372044db99df61f0ed4f7459e,
title = "CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis",
abstract = "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 chemokine-dependent 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.",
keywords = "Animals, Cell Line, Chemokine CXCL5, Inflammation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis, Neutrophil Infiltration, Neutrophils, Pneumocytes, Receptors, Interleukin-8B, T-Lymphocytes, Toll-Like Receptor 2, Transcriptional Activation, Tuberculosis, Pulmonary",
author = "Geraldine Nouailles and Anca Dorhoi and Markus Koch and Jens Zerrahn and January Weiner and Fa{\'e}, {Kellen C} and Frida Arrey and Stefanie Kuhlmann and Silke Bandermann and Delia Loewe and Hans-Joachim Mollenkopf and Alexis Vogelzang and Catherine Meyer-Schwesinger and Hans-Willi Mittr{\"u}cker and Gayle McEwen and Kaufmann, {Stefan H E}",
year = "2014",
month = mar,
day = "3",
doi = "10.1172/JCI72030",
language = "English",
volume = "124",
pages = "1268--82",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",

}

RIS

TY - JOUR

T1 - CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis

AU - Nouailles, Geraldine

AU - Dorhoi, Anca

AU - Koch, Markus

AU - Zerrahn, Jens

AU - Weiner, January

AU - Faé, Kellen C

AU - Arrey, Frida

AU - Kuhlmann, Stefanie

AU - Bandermann, Silke

AU - Loewe, Delia

AU - Mollenkopf, Hans-Joachim

AU - Vogelzang, Alexis

AU - Meyer-Schwesinger, Catherine

AU - Mittrücker, Hans-Willi

AU - McEwen, Gayle

AU - Kaufmann, Stefan H E

PY - 2014/3/3

Y1 - 2014/3/3

N2 - 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 chemokine-dependent 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.

AB - 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 chemokine-dependent 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.

KW - Animals

KW - Cell Line

KW - Chemokine CXCL5

KW - Inflammation

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mycobacterium tuberculosis

KW - Neutrophil Infiltration

KW - Neutrophils

KW - Pneumocytes

KW - Receptors, Interleukin-8B

KW - T-Lymphocytes

KW - Toll-Like Receptor 2

KW - Transcriptional Activation

KW - Tuberculosis, Pulmonary

U2 - 10.1172/JCI72030

DO - 10.1172/JCI72030

M3 - SCORING: Journal article

C2 - 24509076

VL - 124

SP - 1268

EP - 1282

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 3

ER -