During Aspergillus infection, neutrophil, monocyte-derived DC, and plasmacytoid DC enhance innate immune defense through CXCR3-dependent crosstalk

SummaryAspergillus fumigatus, a ubiquitous mold, is a common cause of invasive aspergillosis (IA) in immunocompromised patients. Host defense against IA relies on lung-infiltrating neutrophils and monocyte-derived dendritic cells (Mo-DCs). Here, we demonstrate that plasmacytoid dendritic cells (pDCs), which are prototypically anti-viral cells, participate in innate immune crosstalk underlying mucosal antifungal immunity. Aspergillus-infected murine Mo-DCs and neutrophils recruited pDCs to the lung by releasing the CXCR3 ligands, CXCL9 and CXCL10, in a Dectin-1/Card9- and type I and III interferon-signaling dependent manner, respectively. During aspergillosis, circulating pDCs entered the lung in response to CXCR3-dependent signals. Via targeted pDC ablation, we found that pDCs were essential for host defense in the presence of normal neutrophil and Mo-DC numbers. Although interactions between pDC and fungal cells were not detected, pDCs regulated neutrophil NADPH oxidase activity and conidial killing. Thus, pDCs act as positive feedback amplifiers of neutrophil effector activity against inhaled mold conidia.

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Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella

Journal of Experimental Medicine ◽

10.1084/jem.20100257 ◽

2010 ◽

Vol 207 (8) ◽

pp. 1745-1755 ◽

Cited By ~ 347

Author(s):

Petr Broz ◽

Kim Newton ◽

Mohamed Lamkanfi ◽

Sanjeev Mariathasan ◽

Vishva M. Dixit ◽

...

Keyword(s):

Salmonella Typhimurium ◽

Host Defense ◽

Immune Defense ◽

Innate Immune ◽

Microbial Pathogens ◽

Intracellular Pathogens ◽

Danger Signals ◽

Caspase 1 ◽

Innate Immune Defense

Intracellular pathogens and endogenous danger signals in the cytosol engage NOD-like receptors (NLRs), which assemble inflammasome complexes to activate caspase-1 and promote the release of proinflammatory cytokines IL-1β and IL-18. However, the NLRs that respond to microbial pathogens in vivo are poorly defined. We show that the NLRs NLRP3 and NLRC4 both activate caspase-1 in response to Salmonella typhimurium. Responding to distinct bacterial triggers, NLRP3 and NLRC4 recruited ASC and caspase-1 into a single cytoplasmic focus, which served as the site of pro–IL-1β processing. Consistent with an important role for both NLRP3 and NLRC4 in innate immune defense against S. typhimurium, mice lacking both NLRs were markedly more susceptible to infection. These results reveal unexpected redundancy among NLRs in host defense against intracellular pathogens in vivo.

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TNF/iNOS-Producing Dendritic Cells Mediate Innate Immune Defense against Bacterial Infection

Immunity ◽

10.1016/s1074-7613(03)00171-7 ◽

2003 ◽

Vol 19 (1) ◽

pp. 59-70 ◽

Cited By ~ 808

Author(s):

Natalya V Serbina ◽

Thais P Salazar-Mather ◽

Christine A Biron ◽

William A Kuziel ◽

Eric G Pamer

Keyword(s):

Dendritic Cells ◽

Bacterial Infection ◽

Immune Defense ◽

Innate Immune ◽

Innate Immune Defense

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The Network of Colonic Host Defense Peptides as an Innate Immune Defense Against Enteropathogenic Bacteria

Frontiers in Immunology ◽

10.3389/fimmu.2020.00965 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 4

Author(s):

Graham A. D. Blyth ◽

Liam Connors ◽

Cristina Fodor ◽

Eduardo R. Cobo

Keyword(s):

Host Defense ◽

Immune Defense ◽

Innate Immune ◽

Host Defense Peptides ◽

Enteropathogenic Bacteria ◽

Innate Immune Defense ◽

Defense Peptides

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Faculty Opinions recommendation of TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014553.191924 ◽

2003 ◽

Author(s):

Siamon Gordon

Keyword(s):

Dendritic Cells ◽

Bacterial Infection ◽

Immune Defense ◽

Innate Immune ◽

Innate Immune Defense

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Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1011549108 ◽

2010 ◽

Vol 108 (1) ◽

pp. 278-283 ◽

Cited By ~ 74

Author(s):

Baidong Hou ◽

Alicia Benson ◽

Lili Kuzmich ◽

Anthony L. DeFranco ◽

Felix Yarovinsky

Keyword(s):

Dendritic Cells ◽

Toxoplasma Gondii ◽

Host Defense ◽

Adaptor Protein ◽

T Cell Response ◽

Immune Defense ◽

Innate Immune ◽

Microbial Pathogens ◽

Toll Like Receptors ◽

Inflammatory Monocytes

Toll-like receptors (TLRs) play an important role in host defense against a variety of microbial pathogens. We addressed the mechanism by which TLRs contribute to host defense against the lethal parasite Toxoplasma gondii by using mice with targeted inactivation of the TLR adaptor protein myeloid differentiation primary response gene 88 (MyD88) in different innate cell types. Lack of MyD88 in dendritic cells (DCs), but not in macrophages or neutrophils, resulted in high susceptibility to the T. gondii infection. In the mice deficient in MyD88 in DCs, the early IL-12 response by DCs was ablated, the IFN-γ response by natural killer cells was delayed, and the recruited inflammatory monocytes were incapable of killing the T. gondii parasites. The T-cell response, although attenuated in these mice, was sufficient to eradicate the parasite during the chronic stage, provided that defects in DC activation were compensated by IL-12 treatment early after infection. These results demonstrate a central role of DCs in orchestrating the innate immune response to an intracellular pathogen and establish that defects in pathogen recognition by DCs can predetermine sensitivity to infection.

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