Characterization of IL-22 and antimicrobial peptide production in mice protected against pulmonary Cryptococcus neoformans infection.
Cryptococcus neoformans is a significant cause of fungal meningitis in patients with impaired T cell-mediated immunity (CMI). Experimental pulmonary infection with a C. neoformans strain engineered to produce IFN-γ, H99γ, results in the induction of Th1-type CMI, resolution of the acute infection, and protection against challenge with WT Cryptococcus. Given that individuals with suppressed CMI are highly susceptible to pulmonary C. neoformans infection, we sought to determine whether antimicrobial peptides were produced in mice inoculated with H99γ. Thus, we measured levels of antimicrobial peptides lipocalin-2, S100A8, S100A9, calprotectin (S100A8/A9 heterodimer), serum amyloid A-3 (SAA3), and their putative receptors Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE) in mice during primary and recall responses against C. neoformans infection. Results showed increased levels of IL-17A and IL-22, cytokines known to modulate antimicrobial peptide production. We also observed increased levels of lipocalin-2, S100A8, S100A9 and SAA3 as well as TLR4(+) and RAGE(+) macrophages and dendritic cells in mice inoculated with H99γ compared with WT H99. Similar results were observed in the lungs of H99γ-immunized, compared with heat-killed C. neoformans-immunized, mice following challenge with WT yeast. However, IL-22-deficient mice inoculated with H99γ demonstrated antimicrobial peptide production and no change in survival rates compared with WT mice. These studies demonstrate that protection against cryptococcosis is associated with increased production of antimicrobial peptides in the lungs of protected mice that are not solely in response to IL-17A and IL-22 production and may be coincidental rather than functional.
The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA.|Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA.
Karen L
KL
Wozniak
The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA.|Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA.
Camaron R
CR
Hole
Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Junko
J
Yano
Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Paul L
PL
Fidel
The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA.|Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA.
Floyd L
FL
Wormley
D000209:Acute-Phase Proteins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology* / Q000378:metabolism; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D000097043:Interleukin-22
D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents; D017127:Glycation End Products, Advanced; D020381:Interleukin-17; D007378:Interleukins; D010455:Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D000097043:Interleukin-22; C493487:Tlr4 protein, mouse