Brucella abortus induces TNF and IL-12p40 by MyD88-dependent pathways.

2003 SEP 17 - (NewsRx.com & NewsRx.net) -- Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways.

"Cattle and humans are susceptible to infection with the Gram-negative intracellular bacterium Brucella abortus. Heat-killed B. abortus (HKBA) is a strong Th1 adjuvant and carrier," scientists writing in the Journal of Immunology report.

"Previously, we have demonstrated that dendritic cells produce IL-12 in response to HKBA stimulation," stated Li-Yun Huang and collaborators at the Centers for Disease Control and Prevention, National Cancer Institute, and the University of Massachusetts. "In the present study, we use knockout mice and in vitro reconstitution assays to examine the contribution of signaling by Toll-like receptors (TLRs) and their immediate downstream signaling initiator, myeloid differentiation protein MyD88, in the activation following stimulation by HKBA. Our results show that HKBA-mediated induction of IL-12p40 and TNF is dependent on the adapter molecule MyD88."

"To identify the TLR involved in HKBA recognition, we examined HKBA responses in TLR2- and TLR4-deficient animals," said the researchers. "TNF responses to HKBA were TLR4 independent; however, the response in TLR2-deficient mice was significantly delayed and reduced, although not completely abolished. Studies using Chinese hamster ovary/CD14 reporter cell lines stably transfected with either human TLR2 ...