Browsing by Subject "Phagosomes"

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    Open Access
    Characterisation of innate fungal recognition in the lung
    (Public Library of Science, 2012) Faro-Trindade, Inês; Willment, Janet A; Kerrigan, Ann M; Redelinghuys, Pierre; Hadebe, Sabelo; Reid, Delyth M; Srinivasan, Naren; Wainwright, Helen; Lang, Dirk M; Steele, Chad
    The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus , and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung.
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    Stage-specific sampling by pattern recognition receptors during Candida albicans phagocytosis
    (Public Library of Science, 2008) Heinsbroek, Sigrid E M; Taylor, Philip R; Martinez, Fernando O; Martinez-Pomares, Luisa; Brown, Gordon D; Gordon, Siamon
    Author Summary Infection by Candida albicans has increased as a result of immunosuppression associated with AIDS and organ transplantation. We assessed the role of three pattern recognition receptors, namely Dectin-1 (a beta glucan receptor), the type 3 complement receptor (CR3), and the mannose receptor, in mediating uptake of this fungus. These receptors are known to recognize structures on the C. albicans cell wall, but their exact contribution to binding and uptake is still unclear. We show that only Dectin-1 plays a major role in binding and uptake of C. albicans . Furthermore, we are the first to find that these receptors sample the internalized particle in a sequential manner; intracellular mannose receptor is recruited later and is involved in secretion of immune modulators. These findings provide a better understanding of the innate immune mechanisms involved in protection against this medically important fungal pathogen.