Role of microglia in fungal infections of the central nervous system

Abstract

Most fungi are capable of disseminating into the central nervous system (CNS) commonly being observed in immunocompromised hosts. Microglia play a critical role in responding to these infections regulating inflammatory processes proficient at controlling CNS colonization by these eukaryotic microorganisms. Nonetheless, it is this inflammatory state that paradoxically yields cerebral mycotic meningoencephalitis and abscess formation. As peripheral macrophages and fungi have been investigated aiding our understanding of peripheral disease, ascertaining the key interactions between fungi and microglia may uncover greater abilities to treat invasive fungal infections of the brain. Here, we present the current knowledge of microglial physiology. Due to the existing literature, we have described to greater extent the opportunistic mycotic interactions with these surveillance cells of the CNS, highlighting the need for greater efforts to study other cerebral fungal infections such as those caused by geographically restricted dimorphic and rare fungi.

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

“…CNS aspergillosis generally occurs as a result of direct invasion from adjacent structures or through haematogenous spread. 2,3,38 In the present report, pulmonary or sinus involvement as a possible primary site of infection for CNS IFD was identified in only 58% of patients. However, ibrutinib has good penetration of the blood-brain barrier, attaining free-drug concentrations within fourfold of those in blood.…”

“…The main route of transmission of filamentous fungi is by inhalation of spores into the respiratory tract. CNS aspergillosis generally occurs as a result of direct invasion from adjacent structures or through haematogenous spread . In the present report, pulmonary or sinus involvement as a possible primary site of infection for CNS IFD was identified in only 58% of patients.…”

Neuroinfections caused by fungi

“…The circulating pathogens in the blood must first be arrested in the brain microvasculature and then transmigrate into the brain parenchyma across the blood–brain barrier BBB. Three mechanisms have been described for pathogens to cross the BBB: transcellular migration, paracellular migration, and the Trojan Horse Mechanism [ 11 , 12 ]. Those mechanisms are best understood for Cryptococcus and Candida.…”

The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System

“…Microglia play a vital role in controlling brain tissue colonization by microbes. In spite of their significance, there is limited information on the interactions of these CNS resident cells and C. neoformans [ 59 ]. Studies on the interplay between microglial cells and C. neoformans biofilms are warranted since microglia’s inability to control cryptococcal proliferation and occupation may explain the pathogen’s predilection for the CNS.…”

“…Uncontrolled cryptococcal infection, can lead to the formation of localized CNS lesions or cryptococcomas ( Figure 2 A), a biofilm-like collection of yeast cells entangled in capsular material and characterized by neuronal loss ( Figure 2 B). This cryptococcal lesion, often surrounded by microglia [ 59 ], is an innate immune response typically observed in infected individuals unable to fight against the overwhelming cryptococcal burden ( Figure 2 C). Instead of the microbicidal response, the biofilm-like mass is encased with lymphocytes, macrophages and multinuclear giant cells, resembling a chronic granulomatous reaction ( Figure 2 D) [ 60 ].…”