Differential migration of human monocyte-derived dendritic cells after infection with prevalent clinical strains of Mycobacterium tuberculosis.
Dendritic cells (DCs) play a key role in the host immune response to infections. Mycobacterium tuberculosis (MTB) can inhibit the maturation of DCs and impair their ability to stimulate T cell proliferation. Here, we assessed in vitro migratory behavior of human monocyte-derived DCs (MoDC) when infected with various MTB strains (H37Rv and prevalent clinical strains S7 and S10 from South India). The migration of Rv and S7 infected MoDC towards secondary lymphoid chemokine (CCL21) was 50% lower after 1 day of infection compared to LPS stimulation. This reduced cell migration may be due to a block in the chemokine receptor switch from CCR5 to CCR7 expression on MoDC. Only clinical strain S10 infected MoDC showed an up-regulation of CCR7 and down-regulation of CCR5 expression, similar to LPS stimulated MoDC. While Rv and S7 infected MoDC did not display any alteration in expression of these receptors. Similarly, Rv and S7 infected MoDC did not induce IL-8, IP-10 and MCP-1 chemokine production. This reduction in chemokine levels was reflected in the reduced chemoattraction of CD4(+) T cells also. These findings suggest that there is variation in the stimulation of MoDC with different clinical strains of MTB and this variation may be dependent upon the virulence of the strain.
Rajashree
P
P
Department of Immunology, Tuberculosis Research Centre (ICMR), Mayor VR Ramanathan Road, Chetpet, Chennai 600031, India.
Supriya
P
P
Das
Sulochana D
SD
D000293:Adolescent; D000328:Adult; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D002633:Chemotaxis; D003713:Dendritic Cells / Q000382:microbiology* / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D019713:Receptors, CCR5 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D015854:Up-Regulation; D014774:Virulence
C111835:CCL2 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D016209:Interleukin-8; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine