Recognition mechanism of pathogen-associated molecular patterns and role of innate immune lymphocytes in fungal infection

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3 Citations (Scopus)

Abstract

Cryptoccus neoformans, a yeast-like opportunistic fungal pathogen, causes fatal meningoencephalitis in patients with a compromised immune response, such as AIDS. Host defense against this pathogen is mediated by cellular immunity, and Th1-related cytokines play central roles, whereas Th2 cytokines negatively regulate these responses. When C. neoformans invades host tissues, macrophages and dendritic cells recognize its components, which leads to the activation of innate immune lymphocytes. During this process, the contribution of TLR-2 and TLR-4 is controversial, and in contrast, the interaction of TLR9 with DNA from C. neoformans seems to be deeply involved through a MyD88-dependent signaling pathway. Recently, dectin-1, a C-type lectin receptor, has garnered attention as a sole receptor of beta-1,3-glucan, a major polysaccharide component of the fungal cell wall. However, mice with genetic disruption of this molecule do not show any impairment of the cytokine response and host defense against cryptococcal infection, suggesting that the contribution of dectin-1 is less likely. Following the recognition step, innate immune lymphocytes such as NKT cells and gammadelta T cells are accumulated and activated at the site of infection. Interestingly, NKT cells promote, whereas gammadeltaT cells suppress, Th1-based immune responses and host defense against this infection, as shown by attenuation and promotion of these responses in mice genetically lacking NKT cells and gammadeltaT cells, respectively. Thus, host defense immune responses to C. neoformans infection are critically regulated by recognition of its components through pattern recognition receptors, such as TLR9, and also by competing activities of NKT cells and gammadeltaT cells.

Original languageEnglish
Pages (from-to)779-785
Number of pages7
JournalRinsho byori. The Japanese journal of clinical pathology
Volume57
Issue number8
Publication statusPublished - 2009 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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