Cutaneous host defense in leishmaniasis: interaction of isolated dermal macrophages and epidermal Langerhans cells with the insect-stage promastigote.
Leishmania species are obligate intracellular pathogens of mononuclear phagocytes. Successful infection depends on sequestration of the promastigote (insect form) within host cells, allowing transformation into the relatively hardy amastigote stage. Promastigotes are killed readily by circulating phagocytes and nonimmune serum, suggesting that cutaneous infection is initiated within a permissive cell in the epidermis or dermis. From large sections of primate skin dermal macrophages and epidermal Langerhans cells were isolated, and their interaction with promastigotes of Leishmania major was investigated in vitro. Dermal macrophages were readily infected with promastigotes, and successful transformation to and replication of amastigotes was observed. Ingestion of promastigotes by dermal macrophages was not associated with a significant respiratory burst, in contrast to that by other macrophage populations, and was associated with significantly greater survival of parasites. Stimulation of these cells with phorbol myristate acetate or opsonized zymosan revealed that those cells were generally oxidatively deficient. Langerhans cells could not be successfully infected by promastigotes under similar conditions. Examination of these cells for expression of CR3, which has been identified as a potential Leishmania receptor, revealed that Langerhans cells did not express the alpha M subunit of CR3, whereas dermal macrophages were CR3 positive. These data support the concept that dermal macrophages are the site of initiation of Leishmania infection.
Locksley
R M
RM
Department of Medicine, Seattle Veterans Administration Medical Center, Washington 98108.
Heinzel
F P
FP
Fankhauser
J E
JE
Nelson
C S
CS
Sadick
M D
MD
D000818:Animals; D000911:Antibodies, Monoclonal; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D007111:Immunity, Cellular; D007801:Langerhans Cells / Q000276:immunology*; D007895:Leishmania tropica / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b; D012867:Skin / Q000166:cytology / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D013481:Superoxides