Using bone marrow chimeras, LeibundGut-Landmann et al. conclude in a recent study that nonhematopoietic cells are important to host defense in the lung against an intracellular pathogen, Legionella pneumophila (reviewed in Ref. 1). Neutrophils are a critical contributor to host defense in the lungs (2) because selective depletion of neutrophils results in substantial reduction in the clearance of Klebsiella pneumoniae and L. pneumophila organisms. Using bone marrow chimeras, we have shown that both hematopoietic and nonhematopoietic cells in the lungs are essential for neutrophil-dependent host defense against extracellular pathogens, including Escherichia coli (3) and K. pneumoniae (4). CXCL1/KC, CXCL2/MIP-2, CXCL5/LIX, and lungkine are the primary neutrophil chemokines in mice, and the receptor for these chemokines, CXCR2, is expressed on both hematopoietic and nonhematopoietic cells. KC and MIP-2 are produced by both hematopoietic and nonhematopoietic cells in the lung (2), whereas LIX and lungkine are secreted primarily by nonhematopoietic cells, such as epithelial cells (5, 6). Although the reported findings (1) are conclusive, neutrophil accumulation was measured within 28 h following infection and epithelial chemokines have not been measured. Nonetheless, these findings (1) lead us to wonder whether both hematopoietic and nonhematopoietic cells are important for neutrophil-dependent host defense to extracellular Gram-negative pathogens, or whether one of these cell types is necessary and/or sufficient to induce host defense against intracellular Gram-negative pathogens. These findings will have translational implications for harnessing innate immunity versus targeting the causative bacterium to combat multidrug-resistant bacteria and to develop potent vaccines against pulmonary infections.

1
LeibundGut-Landmann
S.
,
Weidner
K.
,
Hilbi
H.
,
Oxenius
A.
.
2011
.
Nonhematopoietic cells are key players in innate control of bacterial airway infection
.
J. Immunol
.
186:
3130
3137
.
2
Balamayooran
G.
,
Batra
S.
,
Fessler
M. B.
,
Happel
K. I.
,
Jeyaseelan
S.
.
2010
.
Mechanisms of neutrophil accumulation in the lungs against bacteria
.
Am. J. Respir. Cell Mol. Biol
.
43
:
5
16
.
3
Cai
S.
,
Zemans
R. L.
,
Young
S. K.
,
Worthen
G. S.
,
Jeyaseelan
S.
.
2009
.
Myeloid differentiation protein-2-dependent and -independent neutrophil accumulation during Escherichia coli pneumonia
.
Am. J. Respir. Cell Mol. Biol
.
40
:
701
709
.
4
Cai
S.
,
Batra
S.
,
Lira
S. A.
,
Kolls
J. K.
,
Jeyaseelan
S.
.
2010
.
CXCL1 regulates pulmonary host defense to Klebsiella infection via CXCL2, CXCL5, NF-kappaB, and MAPKs
.
J. Immunol
.
185
:
6214
6225
.
5
Jeyaseelan
S.
,
Manzer
R.
,
Young
S. K.
,
Yamamoto
M.
,
Akira
S.
,
Mason
R. J.
,
Worthen
G. S.
.
2005
.
Induction of CXCL5 during inflammation in the rodent lung involves activation of alveolar epithelium
.
Am. J. Respir. Cell Mol. Biol
.
32
:
531
539
.
6
Rossi
D. L.
,
Hurst
S. D.
,
Xu
Y.
,
Wang
W.
,
Menon
S.
,
Coffman
R. L.
,
Zlotnik
A.
.
1999
.
Lungkine, a novel CXC chemokine, specifically expressed by lung bronchoepithelial cells
.
J. Immunol
.
162
:
5490
5497
.