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Polymorphonuclear neutrophils improve replication of Chlamydia pneumoniae in vivo upon MyD88-dependent attraction
Nuria Rodriguez1, Falko Fend, Luise Jennen
1Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Abstract:
Chlamydia pneumoniae, an obligate intracellular bacterium, causes pneumonia in humans and mice. In this study, we show that GR1+/CD45+ polymorphonuclear neutrophils (PMN) surprisingly increase the bacterial load of C. pneumoniae in vivo. Upon intranasal infection of wild-type mice, the lung weight is increased; the cytokines TNF, IL-12p40, and IFN-gamma, as well as the chemokines keratinocyte-derived chemokine, MCP-1, and MIP-2 are secreted; and GR1+/CD45+ PMN are recruited into lungs 3 days postinfection. In contrast, in infected MyD88-deficient mice, which lack a key adaptor molecule in the signaling cascade of TLRs and IL-1R family members, the increase of the lung weight is attenuated, and from the analyzed cyto- and chemokines, only IL-12p40 is detectable. Upon infection, almost no influx of inflammatory cells into lungs of MyD88-deficient mice can be observed. Six days postinfection, however, MyD88-deficient mice were able to produce TNF, IFN-gamma, keratinocyte-derived chemokine, and MCP-1 in amounts similar to wild-type mice, but failed to secrete IL-12p40 and MIP-2. At this time point, the infection increased the lung weight to a level similar to wild-type mice. Curiously, the chlamydial burden in MyD88-deficient mice 3 days postinfection is lower than in wild-type mice, a finding that can be reproduced in wild-type mice by depletion of GR1+ cells. In analyzing how PMN influence the chlamydial burden in vivo, we find that PMN are infected and enhance the replication of C. pneumoniae in epithelial cells. Thus, the lower chlamydial burden in MyD88-deficient mice can be explained by the failure to recruit PMN.
Insights
Polymorphonuclear neutrophils (PMN) surprisingly worsen Chlamydia pneumoniae lung infections by enhancing bacterial replication. Depleting PMN or using MyD88-deficient mice reduces bacterial load, highlighting PMN
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Chlamydia pneumoniae is an intracellular bacterium causing pneumonia.
- Immune responses, including cytokine and chemokine secretion, are crucial in host defense against C. pneumoniae.
- MyD88 is a key adaptor molecule in Toll-like receptor (TLR) and IL-1 receptor signaling pathways.
Purpose of the Study:
- To investigate the role of polymorphonuclear neutrophils (PMN) in C. pneumoniae infection.
- To elucidate the involvement of MyD88 signaling in the host response to C. pneumoniae.
- To understand how PMN influence bacterial load and replication in vivo.
Main Methods:
- Intranasal infection of wild-type and MyD88-deficient mice with C. pneumoniae.
- Measurement of lung weight, cytokine and chemokine levels (TNF, IL-12p40, IFN-gamma, keratinocyte-derived chemokine, MCP-1, MIP-2).
- Analysis of inflammatory cell recruitment (GR1+/CD45+ PMN) and chlamydial burden.
- Experimental depletion of GR1+ cells in wild-type mice.
Main Results:
- Wild-type mice showed increased lung weight, significant cytokine/chemokine secretion, and PMN recruitment post-infection.
- MyD88-deficient mice exhibited attenuated lung weight increase and limited cytokine/chemokine profiles, with minimal inflammatory cell influx.
- Chlamydial burden was lower in MyD88-deficient mice at 3 days post-infection, correlating with reduced PMN recruitment.
- PMN were found to be infected with C. pneumoniae and enhanced its replication in epithelial cells.
Conclusions:
- GR1+/CD45+ PMN unexpectedly increase C. pneumoniae bacterial load in vivo.
- MyD88 signaling is important for early inflammatory responses and PMN recruitment during C. pneumoniae infection.
- The reduced chlamydial burden in MyD88-deficient mice is attributed to their failure to recruit PMN, which enhance bacterial replication.
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