Effects of host response and antifungal therapy on serum and BAL levels of galactomannan and (1→3)-β-D-glucan in experimental invasive pulmonary aspergillosis.

Abstract

Galactomannan and (1→3)-β-D-glucan are useful biomarkers of invasive pulmonary aspergillosis (IPA). However, the effects of immunosuppression on levels of galactomannan or (1→3)-β-D-glucan in IPA are not well understood or quantified. We therefore studied the simultaneous levels of galactomannan and (1→3)-β-D-glucan in two rabbit models of experimental IPA: (1) AraC-induced neutropenia in untreated (UC-AraC) and liposomal amphotericin B-treated (LAMB-AraC) rabbits; and (2) nonneutropenic cyclosporine-methylprednisolone immunosuppression in untreated (UC-CsA+M) and LAMB-treated (LAMB-CsA+M) rabbits. Simultaneous levels of galactomannan and (1→3)-β-D-glucan were determined in bronchoalveolar lavage (BAL) fluid and serial serum specimens and correlated with pulmonary host response. Serum galactomannan index (GMI) and (1→3)-β-D-glucan concentration-time-curves were higher in UC-AraC vs. UC-CsA+M (Mann-Whitney U-test, P < .05). Serum galactomannan and (1→3)-β-D-glucan in treatment groups demonstrated therapeutic responses with similarly lower levels in comparison to UC (P < .01) in both models. Host differences did not affect BAL fluid GMI or (1→3)-β-D-glucan but did affect galactomannan and (1→3)-β-D-glucan levels in serum. The higher serum GMI and (1→3)-β-D-glucan concentration-time-curves in UC-AraC correlated with extensive pulmonary infiltration by angioinvasive hyphae and minimal inflammation, while the lower concentration-time-curves in UC-CsA+M were associated with shorter and fewer hyphae in lung tissue and an intensive neutrophil response to Aspergillus hyphae. Thus, serum levels of galactomannan and (1→3)-β-D-glucan in IPA depended upon immunosuppression, which also affected severity of infection and hyphal morphology, while BAL fluid galactomannan and (1→3)-β-D-glucan were sensitive biomarkers not affected by host response.

• Authors: Ruta Petraitiene, Vidmantas Petraitis, John D Bacher, Malcolm A Finkelman, Thomas J Walsh
• Journal: Medical mycology (Med Mycol) Vol. 53 Issue 6 Pg. 558-68 (Aug 2015) ISSN: 1460-2709 [Electronic] England
• PMID: 26129890 (Publication Type: Journal Article)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antifungal Agents
• Mannans
• Proteoglycans
• beta-Glucans
• galactomannan
• polysaccharide-K
• Galactose

Topics

• Animals
• Antifungal Agents (therapeutic use)
• Bronchoalveolar Lavage Fluid (chemistry, microbiology)
• Disease Models, Animal
• Female
• Galactose (analogs & derivatives)
• Host-Pathogen Interactions
• Invasive Pulmonary Aspergillosis (drug therapy, microbiology, mortality)
• Lung (microbiology, pathology)
• Mannans (analysis, blood)
• Proteoglycans
• Rabbits
• beta-Glucans (analysis, blood)