Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells.
Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasite Leishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro-inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response.
Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
Maira Cegatti
MC
Bosseto
Patricia Vianna Bonini
PV
Palma
Dimas Tadeu
DT
Covas
Selma
S
Giorgio
D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D018664:Interleukin-12 / Q000096:biosynthesis; D007891:Leishmania / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype
D018122:B7-1 Antigen; D018664:Interleukin-12