Monocytes and the Host Response to Fungal Pathogens

Abstract

Monocytes and their derivatives, including macrophages and dendritic cells, play diverse roles in the response to fungal pathogens. Sensing of fungi by monocytes triggers signaling pathways that mediate direct effects like phagocytosis and cytokine production. Monocytes can also present fungal antigens to elicit adaptive immune responses. These monocyte-mediated pathways may be either beneficial or harmful to the host. In some instances, fungi have developed mechanisms to evade the consequences of monocyte activation and subvert these cells to promote disease. Thus, monocytes are critically involved in mediating the outcomes of these often highly fatal infections. This review will highlight the roles of monocytes in the immune response to some of the major fungi that cause invasive human disease, including Aspergillus, Cryptococcus, Candida, Histoplasma, Blastomyces, and Coccidioides, and discuss potential strategies to manipulate monocyte responses in order to enhance anti-fungal immunity in susceptible hosts.

The Dual Function of the Fungal Toxin Candidalysin during Candida albicans—Macrophage Interaction and Virulence

“…Tissue-resident macrophages are needed for innate immune defense against C. albicans infections [ 12 ]. Patrolling monocytes migrate into infected tissues and differentiate into macrophages and dendritic cells, with the latter bridging innate and adaptive immunity against C. albicans by presenting fungal antigens to naive T-cells in lymph nodes [ 32 , 33 ]. Monocytes and macrophages contribute directly to fungal clearance by internalization and subsequent intracellular killing, but they also mediate neutrophil recruitment [ 14 , 16 , 17 , 18 ].…”

Modulation of Immune Responses by Particle Size and Shape

“…They are more equipped to phagocytose smaller morphological states of fungi; larger hyphae or spores sometimes cannot be taken up by macrophages ( 7 – 9 ). Macrophages can polarize into pro-inflammatory (M1) phenotypes if activated by pro-inflammatory stimuli such as interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), or microbial stimuli such as lipopolysaccharide (LPS) ( 10 ). Alternatively, macrophages can polarize into anti-inflammatory homeostatic (M2) phenotypes induced by anti-inflammatory cytokines interleukin (IL)-4 or IL-13 ( 10 ).…”

“…Macrophages can polarize into pro-inflammatory (M1) phenotypes if activated by pro-inflammatory stimuli such as interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), or microbial stimuli such as lipopolysaccharide (LPS) ( 10 ). Alternatively, macrophages can polarize into anti-inflammatory homeostatic (M2) phenotypes induced by anti-inflammatory cytokines interleukin (IL)-4 or IL-13 ( 10 ). The shift from M2 to M1-like phenotypes is associated with more microbicidal activity of macrophages ( 10 ).…”

Oral Administration of Lactobacillus helveticus LA401 and Lactobacillus gasseri LA806 Combination Attenuates Oesophageal and Gastrointestinal Candidiasis and Consequent Gut Inflammation in Mice

“…Given the major regulatory role of cytokines in the immune response against fungal pathogens [ 40 ], we evaluated the ability of LA401 and/or LA806 strains to modulate the expression of pro- and anti-inflammatory cytokines and chemokines in IFN-γ/LPS-activated macrophages. LA401 and/or LA806 increased the mRNA and protein expression of the pro-inflammatory cytokines IL-12, TNF-α, IL-1β and IL-6, as well as the chemokine CCL2 ( Figure 6 a,b), suggesting that LA401 and/or LA806 promote antifungal host defense through their ability to modulate the release of pro-inflammatory mediators involved in the protection against fungal pathogens by macrophages.…”

“…However, high level of Candida colonization is associated with several digestive diseases and appears to exacerbate inflammation [ 5 ]. Previous studies have reported that probiotics are potentially promising for the prevention or treatment of Candida infections [ 17 , 40 ] and that different Lactobacillus species can affect the immunomodulatory ability of various cellular components of the mucosal immune system [ 41 ].…”