The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides

Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host-fungus interactions in mammals.

Immunity to fungal infections

The IL-10 family of cytokines consists of nine members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. Evolutionarily, IL-10 family cytokines emerged before the adaptive immune response. These cytokines elicit diverse host defense mechanisms, especially from epithelial cells, during various infections. IL-10 family cytokines are essential for maintaining the integrity and homeostasis of tissue epithelial layers. Members of this family can promote innate immune responses from tissue epithelia to limit the damage caused by viral and bacterial infections. These cytokines can also facilitate the tissue-healing process in injuries caused by infection or inflammation. Finally, IL-10 itself can repress proinflammatory responses and limit unnecessary tissue disruptions caused by inflammation. Thus, IL-10 family cytokines have indispensable functions in many infectious and inflammatory diseases.

Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease

Spleen tyrosine kinase (SYK) is known to have a crucial role in adaptive immune receptor signalling. However, recent reports indicate that SYK also mediates other, unexpectedly diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development. SYK is activated by C-type lectins and integrins, and activates new targets, including the CARD9-BCL-10-MALT1 pathway and the NLRP3 inflammasome. Studies using Drosophila melanogaster suggest that there is an evolutionarily ancient origin of SYK-mediated signalling. Moreover, SYK has a crucial role in autoimmune diseases and haematological malignancies. This Review summarizes our current understanding of the diverse functions of SYK and how this is being translated for therapeutic purposes.

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The SYK tyrosine kinase: a crucial player in diverse biological functions.

Immunity to Fungal Infections

The recognition of carbohydrate moieties by cells of the innate immune system is emerging as an essential element in antifungal immunity, but despite the number and diversity of lectins expressed by innate immune cells, few carbohydrate receptors have been characterized. Mincle, a C-type lectin, is expressed predominantly on macrophages, and is here shown to play a role in macrophage responses to the yeast Candida albicans. After exposure to the yeast in vitro, Mincle localized to the phagocytic cup, but it was not essential for phagocytosis. In the absence of Mincle, production of TNF-alpha by macrophages was reduced, both in vivo and in vitro. In addition, mice lacking Mincle showed a significantly increased susceptibility to systemic candidiasis. Thus, Mincle plays a novel and nonredundant role in the induction of inflammatory signaling in response to C. albicans infection.

The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans

The recognition of carbohydrate moieties by cells of the innate immune system is emerging as an essential element in anti-fungal immunity, but few carbohydrate receptors have been characterised, despite the number and diversity of lectins expressed by innate immune cells. We demonstrate a novel role for the c-type lectin Mincle in macrophage responses to C. albicans. Mincle was observed to localise in the phagocytic cup of macrophages in response to a range of stimuli. Loss of Mincle reduced macrophage TNF production both in vivo and in vitro, but did not alter the number of Candida yeast phagocytised. Mice lacking Mincle showed a significantly increased susceptibility to systemic candidiasis. Thus Mincle contributes a novel and non-redundant role in the induction of inflammatory signalling in response to C. albicans infection.

The Macrophage Inducible c-type lectin, Mincle, is an essential component of the innate-immune response to Candida albicans

https://espace.library.uq.edu.au/view/UQ:9179/MicrobRev.pdf

Production and function of cytokines in natural and acquired immunity to Candida albicans infection.

Macrophages are large mononuclear phagocytes that represent the major differentiated elements of the mononuclear phagocytic system. They arise from distinct progenitors in the bone marrow, and their immediate precursors, the monocytes, emigrate from the vascular compartment into many tissues and organs where they develop into mature macrophages. The latter display diverse morphological and functional characteristics, depending on the environmental stimuli that they receive. This phenotypic heterogeneity is, therefore, the final consequence of a series of down-regulation of some cellular processes and the up-regulation of others. The kinetics of the production of macrophages and their participation in various physiological and pathological phenomena is the subject of this review.

Macrophages: Current Views on Their Differentiation, Structure, and Function

Human peripheral blood mononuclear cells which mediate antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus- (HSV) infected target cells consist of both adherent (MA) and nonadherent (MNA) effector cell populations. These two cell populations can be distinguished by their different phagocytic properties and morphologic appearance, their requirement for antibody in the ADCC reaction, and the rapidity with which they lyse target cells in the presence of immune serum. The MA cells are predominantly phagocytic and have the morphologic characteristics of monocyte-macrophages, whereas the MNA cells are nonphagocytic and appear to be small to medium-sized lymphocytes. Optimal expression of ADCC by MA cells requires higher concentrations of immune serum than does MNA cell-mediated ADCC. MA-mediated cell killing is first detectable by 8 hr and reaches completion after 24 hr of incubation. In contrast, MNA-mediated ADCC produces target cell damage by 2 hr and reaches completion at 8 hr of incubation. Unlike MNA effector cells, the MA effector cells are profoundly inhibited after preincubation with either latex or silica particles. The HSV immune status of the donor had no effect on the ability of either cell population to mediate ADCC. These data demonstrate the participation of both nonadherent mononuclear cells, presumably K cells, and monocyte-macrophages, in ADCC directed against HSV-infected target cells.

Robert B. Ashman

Papers

The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans

The Macrophage Inducible c-type lectin, Mincle, is an essential component of the innate-immune response to Candida albicans

Production and function of cytokines in natural and acquired immunity to Candida albicans infection.

Macrophages: Current Views on Their Differentiation, Structure, and Function

Human Monocyte-Macrophage-Mediated Antibody-Dependent Cytotoxicity to Herpes Simplex Virus-Infected Cells