Transforming growth factor-beta expression by host cells is elicited locally by the filarial nematode Onchocerca volvulus in hyporeactive patients independently from Wolbachia.
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Transforming growth factor-beta expression by host cells is elicited locally by the filarial nematode Onchocerca volvulus in hyporeactive patients independently from Wolbachia. / Korten, Simone; Kaifi, Jussuf; Büttner, Dietrich W; Hoerauf, Achim.
in: MICROBES INFECT, Jahrgang 12, Nr. 7, 7, 2010, S. 555-564.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Transforming growth factor-beta expression by host cells is elicited locally by the filarial nematode Onchocerca volvulus in hyporeactive patients independently from Wolbachia.
AU - Korten, Simone
AU - Kaifi, Jussuf
AU - Büttner, Dietrich W
AU - Hoerauf, Achim
PY - 2010
Y1 - 2010
N2 - Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local release of immunosuppressive cytokines. Therefore, using immunohistology, we investigated the expression of stable, released latent TGF-beta1 in subcutaneous nodules from highly infected, hyporeactive onchocerciasis patients, harbouring adult Onchocerca volvulus. Since many cell types produce TGF-beta, we elucidated the cellular source, distribution and dependency on the worms' sex, productivity and vitality. We found TGF-beta1 to be abundantly expressed by T cells, plasma/B cells, macrophages, mast cells, fibrocytes, and vascular endothelial cells, particularly in onchocercomas with productive or previously productive females, damaged, dead and resorbed adult worms or microfilariae. We conclude TGF-beta to be antigen induced by the filariae since expression was scarce around subcutaneous arthropods or cholesterol crystals in onchocercomas. Enhanced expression after ivermectin or endobacteria-depleting doxycycline treatment indicates induction to depend on filariae and not on Wolbachia endobacteria. TGF-beta(+) cells were reduced in HIV co-infection. This finding of local and sustained TGF-beta induction by vital and dead filariae, untreated and after treatment, adds new aspects to immunomodulation by helminths.
AB - Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local release of immunosuppressive cytokines. Therefore, using immunohistology, we investigated the expression of stable, released latent TGF-beta1 in subcutaneous nodules from highly infected, hyporeactive onchocerciasis patients, harbouring adult Onchocerca volvulus. Since many cell types produce TGF-beta, we elucidated the cellular source, distribution and dependency on the worms' sex, productivity and vitality. We found TGF-beta1 to be abundantly expressed by T cells, plasma/B cells, macrophages, mast cells, fibrocytes, and vascular endothelial cells, particularly in onchocercomas with productive or previously productive females, damaged, dead and resorbed adult worms or microfilariae. We conclude TGF-beta to be antigen induced by the filariae since expression was scarce around subcutaneous arthropods or cholesterol crystals in onchocercomas. Enhanced expression after ivermectin or endobacteria-depleting doxycycline treatment indicates induction to depend on filariae and not on Wolbachia endobacteria. TGF-beta(+) cells were reduced in HIV co-infection. This finding of local and sustained TGF-beta induction by vital and dead filariae, untreated and after treatment, adds new aspects to immunomodulation by helminths.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Host-Parasite Interactions
KW - Anti-Bacterial Agents therapeutic use
KW - Antiparasitic Agents therapeutic use
KW - Doxycycline therapeutic use
KW - Endothelium metabolism
KW - HIV Infections complications
KW - Ivermectin therapeutic use
KW - Lymphocytes metabolism
KW - Macrophages metabolism
KW - Mast Cells metabolism
KW - Onchocerca volvulus physiology
KW - Onchocerciasis drug therapy
KW - Rickettsiaceae Infections complications
KW - Transforming Growth Factor beta metabolism
KW - Wolbachia
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Host-Parasite Interactions
KW - Anti-Bacterial Agents therapeutic use
KW - Antiparasitic Agents therapeutic use
KW - Doxycycline therapeutic use
KW - Endothelium metabolism
KW - HIV Infections complications
KW - Ivermectin therapeutic use
KW - Lymphocytes metabolism
KW - Macrophages metabolism
KW - Mast Cells metabolism
KW - Onchocerca volvulus physiology
KW - Onchocerciasis drug therapy
KW - Rickettsiaceae Infections complications
KW - Transforming Growth Factor beta metabolism
KW - Wolbachia
M3 - SCORING: Zeitschriftenaufsatz
VL - 12
SP - 555
EP - 564
JO - MICROBES INFECT
JF - MICROBES INFECT
SN - 1286-4579
IS - 7
M1 - 7
ER -
