PMID- 25161111 OWN - NLM STAT- MEDLINE DCOM- 20150626 LR - 20161020 IS - 1769-714X (Electronic) IS - 1286-4579 (Linking) VI - 16 IP - 9 DP - 2014 Sep TI - Monoclonal antibodies to heat shock protein 60 induce a protective immune response against experimental Paracoccidioides lutzii. PG - 788-95 LID - S1286-4579(14)00104-X [pii] LID - 10.1016/j.micinf.2014.08.004 [doi] AB - Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America. PCM is primarily caused by Paracoccidioides brasiliensis and less frequently by the recently described, closely related species Paracoccidioides lutzii. Current treatment requires protracted administration of systemic antibiotics and relapses may frequently occur despite months of initial therapy. Hence, there is a need for innovative approaches to treatment. In the present study we analyzed the impact of two monoclonal antibodies (mAbs) generated against Heat Shock 60 (Hsp60) from Histoplasma capsulatum on the interactions of P. lutzii with macrophages and on the experimental P. lutzii infection. We demonstrated that the Hsp60-binding mAbs labeled P. lutzii yeast cells and enhanced their phagocytosis by macrophage cells. Treatment of mice with the mAbs to Hsp60 before infection reduced the pulmonary fungal burden as compared to mice treated with irrelevant mAb. Hence, mAbs raised to H. capsulatum Hsp60 are protective against P. lutzii, including mAb 7B6 which was non-protective against H. capsulatum, suggesting differences in their capacity to bind to these fungi and to be recognized by macrophages. These findings indicate that mAbs raised to one dimorphic fungus may be therapeutic against additional dimorphic fungi, but also suggests that biological differences in diseases may influence whether a mAb is beneficial or harmful. CI - Copyright (c) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. FAU - Thomaz, Luciana AU - Thomaz L AD - Institute of Biomedical Sciences, Department of Microbiology, Brazil. Electronic address: lucithomaz@usp.br. FAU - Nosanchuk, Joshua D AU - Nosanchuk JD AD - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. FAU - Rossi, Diego C P AU - Rossi DC AD - Institute of Biomedical Sciences, Department of Microbiology, Brazil. FAU - Travassos, Luiz R AU - Travassos LR AD - Department of Microbiology, Immunology and Parasitology, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Taborda, Carlos P AU - Taborda CP AD - Institute of Biomedical Sciences, Department of Microbiology, Brazil; Laboratory of Medical Mycology IMTSP- LIM53 University of Sao Paulo, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140824 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, Fungal) RN - 0 (Chaperonin 60) RN - 0 (Cytokines) SB - IM MH - Animals MH - Antibodies, Monoclonal/immunology/*therapeutic use MH - Antigens, Fungal/immunology MH - Cells, Cultured MH - Chaperonin 60/*immunology MH - Cytokines/biosynthesis MH - Histoplasma/immunology MH - Liver/microbiology MH - Lung/pathology MH - Mice MH - Mice, Inbred BALB C MH - Paracoccidioides MH - Paracoccidioidomycosis/drug therapy/*immunology/pathology MH - Spleen/microbiology OTO - NOTNLM OT - Hsp60 OT - Monoclonal antibody OT - Paracoccidioides lutzii EDAT- 2014/08/28 06:00 MHDA- 2015/06/27 06:00 CRDT- 2014/08/28 06:00 PHST- 2013/09/16 00:00 [received] PHST- 2014/07/23 00:00 [revised] PHST- 2014/08/06 00:00 [accepted] PHST- 2014/08/28 06:00 [entrez] PHST- 2014/08/28 06:00 [pubmed] PHST- 2015/06/27 06:00 [medline] AID - S1286-4579(14)00104-X [pii] AID - 10.1016/j.micinf.2014.08.004 [doi] PST - ppublish SO - Microbes Infect. 2014 Sep;16(9):788-95. doi: 10.1016/j.micinf.2014.08.004. Epub 2014 Aug 24.