A method for treating a human infected with Aspergillus by using thymosin alpha 1 as an immuno-stimulator in activating dendritic cells. The method is particularly useful in preventing an infection by Aspergillus in an immuno-compromised host being treated with a bone marrow transplantation.
1. A method of treating a fungal infection in a bone marrow transplant recipient comprising administering to said transplant recipient in need thereof a pharmaceutical composition comprising an antifungal effective amount of thymosin alpha 1 (TA1), wherein the antifungal effective amount of thymosin alpha 1 (TA1) induces activity selected from p38 activation, NFkB activation, TLR signaling, MyD88 signaling and dendritic cell activation.
2. The method according to claim 1 , wherein said TA1 is administered at a dose of 200 to 400 micrograms/kg body weight/day.
3. The method according to claim 1 , wherein the TLR signaling induced results in dendritic cell activation.
4. The method according to claim 3 , wherein the dendritic cells are selected from plasmocytoid dendritic cells (PDCs) and myeloid dendritic cells (MDCs).
5. The method according to claim 1 , wherein the MyD88 signaling induced results in dendritic cell activation.
6. The method according to claim 1 , wherein said TA1 is administered at a dose sufficient to produce Th1 cell promoting cytokines.
7. The method according to claim 6 , wherein the Th1 cell promoting cytokines are selected from IL-12 p70, IL-10 and IFN-alpha.
8. The method according to claim 1 , wherein the p38 activation induced is phosphorylation of p38.
9. The method according to claim 1 , wherein the NFkB activation induced is nuclear translocation of NFkB.
10. The method according to claim 1 , wherein said TLR signaling is selected from TLR9 signaling and TLR2 signaling.
11. The method according to claim 10 , wherein said TLR9 signaling results in IL-12 p70 production.
12. The method according to claim 10 , wherein said TLR9 signaling results in activation of plasmocytoid dendritic cells (PDCs).
13. The method according to claim 10 , wherein said TLR2 signaling results in IL-10 and IFN-alpha production.
14. The method according to claim 10 , wherein said TLR2 signaling results in activation of myeloid dendritic cells (MDCs).
15. The method according to claim 1 , wherein the anti-fungal infection is an Aspergillus infection.
16. The method according to claim 15 , wherein said Aspergillus infection is Invasive Aspergillosis.
17. The method according to claim 1 , wherein said bone marrow transplant recipient is a mammal.
18. The method according to claim 1 , wherein said bone marrow transplant recipient is a human.
19. The method according to claim 1 , wherein the method further comprises administering to said recipient at least one additional antifungal agent.
20. The method according to claim 19 , wherein the additional antifungal agent is Amphotericin B.
21. The method according to claim 20 , wherein said Amphotericin B is administered at a dose of 4000 micrograms/kg body weight/day.