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

Ruta Petraitiene, Vidmantas Petraitis, John D. Bacher, Malcolm A. Finkelman, Thomas J. Walsh

Research output: Contribution to journalArticlepeer-review

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-Dglucan 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.

Original languageEnglish (US)
Pages (from-to)558-568
Number of pages11
JournalMedical mycology
Volume53
Issue number6
DOIs
StatePublished - Aug 1 2015

Keywords

  • (1→3)-β-D-glucan
  • Aspergillosis
  • Galactomannan
  • Immunosuppression
  • Neutropenia

ASJC Scopus subject areas

  • Infectious Diseases

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