Dynamic interplay among monocyte-derived, dermal, and resident lymph node dendritic cells during the generation of vaccine immunity to fungi.

Cell and Molecular Pathology Graduate Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Cell host & microbe (Impact Factor: 12.19). 06/2010; 7(6):474-87. DOI: 10.1016/j.chom.2010.05.010
Source: PubMed

ABSTRACT Early innate events that enable priming of antifungal CD4 T cells are poorly understood. We engineered an attenuated fungal vaccine with a model epitope, EalphaRFP, to track vaccine immunity to Blastomyces dermatitidis during yeast recognition, antigen presentation, and priming of naive T cells. After subcutaneous injection of the vaccine, monocyte-derived inflammatory dendritic cells (DCs) are the earliest and largest population that associates with yeast, carrying them into the draining lymph nodes. Despite marked association with yeast, these DCs fail to display surface peptide:MHC complexes or prime naive T cells. Instead, the ability to display antigen and prime CD4 T cells resides with lymph node-resident DCs after antigen transfer from immigrant DCs and with skin migratory DCs. Our work reveals the dynamic interplay among distinct DC subsets that prime naive CD4 T cells after yeast are injected in the skin and discloses the cellular elements underlying vaccine-induced immunity to fungi.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of fungal infections has been on the rise over several decades. Fungal infections threaten animals, plants and humans alike and are thus of significant concern to scientists across disciplines. Over the last decade, significant advances on fungal immunology have lead to a better understanding of important mechanisms of host protection against fungi. In this article, I review recent advances of relevant mechanisms of immune-mediated protection to fungal infections.
    Parasite Immunology 09/2014; 36(9). DOI:10.1111/pim.12098 · 1.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fungal diseases represent an important paradigm in immunology since they can result from either the lack of recognition or over-activation of the inflammatory response. Current understanding of the pathophysiology underlying fungal infections and diseases highlights the multiple cell populations and cell-signaling pathways involved in these conditions. A systems biology approach that integrates investigations of immunity at the systems-level is required to generate novel insights into this complexity and to decipher the dynamics of the host-fungus interaction. It is becoming clear that a three-way interaction between the host, microbiota, and fungi dictates the types of host-fungus relationship. Tryptophan metabolism helps support this interaction, being exploited by the mammalian host and commensals to increase fitness in response to fungi via resistance and tolerance mechanisms of antifungal immunity. The cellular and molecular mechanisms that provide immune homeostasis with the fungal biota and its possible rupture in fungal infections and diseases will be discussed within the expanding role of antifungal Th cell responses.
    Frontiers in Immunology 10/2014; 5:506. DOI:10.3389/fimmu.2014.00506
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monocytes are a subset of circulating blood cells with remarkable plasticity. They can develop into a wide range of terminally differentiated cells and perform versatile functions during infection, tumor formation and in the setting of chronic inflammation. This review focuses on the role of monocytes during microbial infection and summarizes our understanding of the diverse roles that monocytes play in defense against different pathogens.
    Immunobiology 08/2014; 220(2). DOI:10.1016/j.imbio.2014.08.007 · 3.18 Impact Factor


Available from