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Updated: Apr 12, 2026
Author Spotlight: Investigating the Key Factors of Obliterative Bronchiolitis After Lung Transplantation
Published on: November 10, 2023
Sugar polymers exacerbate lung GVHD
Nathan Mathewson1, Pavan Reddy1
1UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER.
Abstract:
In this issue of Blood, Uryu et al demonstrate that recognition of a fungal cell wall component, α-mannan (Mn), an Mn (sugar) polymer, by the C-type lectin receptor Dectin-2 on host macrophages leads to a lung chemokine environment conducive to donor T helper (Th)17 accumulation resulting in severe pulmonary graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). These findings shed new light on a long-standing gap in our understanding of the mechanistic link between infections, specifically fungal, and GVHD severity following allo-HSCT.
Insights
Fungal alpha-mannan recognition by Dectin-2 on macrophages promotes T helper 17 cell accumulation, worsening pulmonary graft-versus-host disease (GVHD) after stem cell transplants. This links fungal infections to severe GVHD outcomes.
Area of Science:
- Immunology
- Microbiology
- Transplantation
Background:
- Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- The role of fungal infections in modulating GVHD severity remains incompletely understood.
- C-type lectin receptors on immune cells play critical roles in pathogen recognition and immune responses.
Purpose of the Study:
- To investigate the mechanistic link between fungal components and GVHD severity.
- To elucidate the role of Dectin-2 in the context of fungal exposure and allo-HSCT.
- To understand how fungal recognition influences the lung immune environment post-allo-HSCT.
Main Methods:
- Utilized mouse models of allo-HSCT.
- Administered alpha-mannan (Mn), a fungal cell wall component.
- Assessed lung chemokine environment and T helper 17 (Th17) cell accumulation.
- Analyzed Dectin-2 expression and function on host macrophages.
Main Results:
- Recognition of alpha-mannan by Dectin-2 on macrophages induced a pro-inflammatory lung chemokine milieu.
- This environment promoted the accumulation of donor T helper 17 (Th17) cells.
- Increased Th17 cell infiltration correlated with severe pulmonary GVHD following allo-HSCT.
Conclusions:
- Fungal alpha-mannan recognition via Dectin-2 is a key mechanism linking fungal infections to severe pulmonary GVHD.
- Host macrophage response to fungal components significantly impacts allo-HSCT outcomes.
- These findings provide a mechanistic basis for understanding fungal infection-associated GVHD severity.
