PMID- 14982877
OWN - NLM
STAT- MEDLINE
DCOM- 20040708
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 11
DP  - 2004 Jun 1
TI  - Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through 
      toll-like receptor signaling.
PG  - 4232-9
AB  - Dendritic cells (DCs) show a remarkable functional plasticity in the recognition 
      of Aspergillus fumigatus and orchestrate the antifungal immune resistance in the 
      lungs. Here, we show that thymosin alpha 1, a naturally occurring thymic peptide, 
      induces functional maturation and interleukin-12 production by fungus-pulsed DCs 
      through the p38 mitogen-activated protein kinase/nuclear factor 
      (NF)-kappaB-dependent pathway. This occurs by signaling through the myeloid 
      differentiation factor 88-dependent pathway, involving distinct Toll-like 
      receptors. In vivo, the synthetic peptide activates T-helper (Th) cell 
      1-dependent antifungal immunity, accelerates myeloid cell recovery, and protects 
      highly susceptible mice that received hematopoietic transplants from 
      aspergillosis. By revealing the unexpected activity of an old molecule, our 
      finding provides the rationale for its therapeutic utility and qualify the 
      synthetic peptide as a candidate adjuvant promoting the coordinated activation of 
      the innate and adaptive Th immunity to the fungus.
FAU - Romani, Luigina
AU  - Romani L
AD  - Department of Experimental Medicine and Biochemical Sciences Microbiology 
      Section, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. 
      lromani@unipg.it
FAU - Bistoni, Francesco
AU  - Bistoni F
FAU - Gaziano, Roberta
AU  - Gaziano R
FAU - Bozza, Silvia
AU  - Bozza S
FAU - Montagnoli, Claudia
AU  - Montagnoli C
FAU - Perruccio, Katia
AU  - Perruccio K
FAU - Pitzurra, Lucia
AU  - Pitzurra L
FAU - Bellocchio, Silvia
AU  - Bellocchio S
FAU - Velardi, Andrea
AU  - Velardi A
FAU - Rasi, Guido
AU  - Rasi G
FAU - Di Francesco, Paolo
AU  - Di Francesco P
FAU - Garaci, Enrico
AU  - Garaci E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040224
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptors)
RN  - 61512-21-8 (Thymosin)
RN  - W0B22ISQ1C (Thymalfasin)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Differentiation/metabolism
MH  - Aspergillosis/*immunology
MH  - Aspergillus fumigatus/*immunology
MH  - Bone Marrow Transplantation
MH  - Dendritic Cells/*immunology/metabolism/microbiology
MH  - Female
MH  - Membrane Glycoproteins/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88
MH  - Receptors, Cell Surface/immunology/*metabolism
MH  - Receptors, Immunologic/metabolism
MH  - Signal Transduction/immunology
MH  - Th1 Cells/*immunology/microbiology
MH  - Thymalfasin
MH  - Thymosin/*analogs & derivatives/immunology/*metabolism
MH  - Toll-Like Receptors
EDAT- 2004/02/26 05:00
MHDA- 2004/07/09 05:00
CRDT- 2004/02/26 05:00
PHST- 2004/02/26 05:00 [pubmed]
PHST- 2004/07/09 05:00 [medline]
PHST- 2004/02/26 05:00 [entrez]
AID - S0006-4971(20)55420-7 [pii]
AID - 10.1182/blood-2003-11-4036 [doi]
PST - ppublish
SO  - Blood. 2004 Jun 1;103(11):4232-9. doi: 10.1182/blood-2003-11-4036. Epub 2004 Feb 
      24.