Aspergillus fumigatusconidia upregulates NOD2 protein expression bothin vitroandin vivo¹

Abstract

Aim: To determine if NOD2 is involved in host recognition of Aspergillus fumigatus (Af) conidia. Methods: An Af conidia pulmonary infection murine model was established by intranasal inoculation of Af conidia suspensions. Protein levels of NOD2 in lung tissue were determined by immunohistochemistry. A549 and phorbol-12-myristate 13-acetate (PMA)-activated THP-1 cell lines were treated with heat-killed Af conidia, then the presence of NOD2 protein in these cell lines was detected by Western blotting. The ability of muramyl dipeptide (MDP) to induce the secretion of TNF-α after incubation with heatkilled Af conidia was measured by enzyme-linked immunosorbent assay.

Tissue‐resident innate immunity in the lung

“…33,34 In humans, MARCO polymorphisms that reduce phagocytic capacity in monocyte-derived macrophages are linked to tuberculosis susceptibility, 33 and lower MARCO expression on AMs from diabetic mice reduces their ability to phagocytose M. tuberculosis. [36][37][38] During infection, AMs still play an important role in limiting inflammation, which could otherwise be fatal. [36][37][38] During infection, AMs still play an important role in limiting inflammation, which could otherwise be fatal.…”

Homozygous carrier of the NOD2 1007fs frame‐shift mutation presenting with refractory community‐acquired spontaneous bacterial peritonitis and developing fatal pulmonary mucormycosis: A case report

“…Whereas a regular neutrophil function of neutrophils and macrophages provides sufficient immune protection against Mucor , patients with alterations of the innate immune defense, as with diabetes mellitus 40 or chronic renal failure, 39 are particularly vulnerable to mucormycosis. Two studies have addressed the role of NOD2 in fungal infections, in particular Aspergillus fumigatus and Candida albicans , with inconclusive results 41,42 . Although NOD2 may not directly detect fungal antigens, there is an extensive interplay between NOD2 and the membranous Toll‐like receptors (TLR)2, 3 and 4 43 that are important for neutrophil activation in fungal infections 44 suggesting a relevance of NOD2 in the immune response towards mycoses.…”

Phagocyte responses towards Aspergillus fumigatus

“…The recognition of fungal PAMPs by either TLRs (Meier et al, 2003) or Dectin-1 (Gersuk et al, 2006) leads to uptake of the spores. Intracellularly other receptors like NOD-2, a member of the NLR family (nucleotide-binding domain, leucine-rich repeatcontaining protein) (Dubourdeau et al, 2006;Zhang et al, 2008) can ultimately initiate MyD88-dependent or -independent mitogenactivated protein kinase (MAPK) signaling pathways, leading to the synthesis of a variety of proinflammatory cytokines like TNF-␣, IL-12, IFN-␥, IL-18, IL-6, IL-1␤, GM-CSF, MIP-1␣, MCP-1, MIP-2 and KC (Duong et al, 1998;Balloy et al, 2005) by AMs. Expression of these cytokine genes is controlled by the transcription factors NF-B (Zhao and Wu, 2008), AP-1 (Toyotome et al, 2008) and IRF3 and the expression of several cytokines changes significantly under immunosuppressive conditions with cortisol (Duong et al, 1998;Balloy et al, 2005).…”