A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensis infection.
BACKGROUND
The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite.


RESULTS
The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells.


CONCLUSIONS
The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells.
Laboratório de Genômica Funcional, Instituto Carlos Chagas, ICC-FIOCRUZ,Paraná, Brazil.
Christian M
CM
Probst
Rodrigo A
RA
Silva
Juliana P B
JP
Menezes
Tais F
TF
Almeida
Ivana N
IN
Gomes
Andréia C
AC
Dallabona
Luiz S
LS
Ozaki
Gregory A
GA
Buck
Daniela P
DP
Pavoni
Marco A
MA
Krieger
Patrícia S T
PS
Veras
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D007894:Leishmania mexicana / Q000276:immunology* / Q000472:pathogenicity*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction