Neuroinflammation in neurodegeneration via microbial infections

Abstract

Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are still not clear due to the biological complexity of multicellular and multiorgan interactions upon microbial infections. In this review, we show the infection leading to neurodegeneration mediated by multiorgan interconnections and neuroinflammation. Firstly, we highlight three inter-organ communications as possible routes from infection sites to the brain: nose-brain axis, lung-brain axis, and gut-brain axis. Next, we described the biological crosstalk between microglia and astrocytes upon pathogenic infection. Finally, our study indicates how neuroinflammation is a critical player in pathogen-mediated neurodegeneration. Taken together, we envision that antibiotics targeting neuro-pathogens could be a potential therapeutic strategy for neurodegeneration.

Keywords: infection; multi-organ; neurodegeneration; neuroinflammation; pathogen.

Figure 1

The inter-organ communication for pathogens to enter the brain. (i) Nose-brain axis is the first possible pathway that allows infectious agents to invade the CNS. Nasal pathogens can reach the brain by bypassing the blood-brain barrier (BBB) as well as the cerebrospinal fluid barrier. Infectious agents can invade the CNS via olfactory sensory neurons lying within the mucosal layer. (ii) Lung-brain axis: Pulmonary microbes and their soluble components may directly disrupt the lung alveolar-capillary barrier to enter the blood or interact with the local immune system, subsequently reaching the CNS by disrupting the BBB. (iii) Gut-brain axis serves as another compromising physiological distance connecting the gut and the brain through blood circulation and the vagus nerve. Bacteria and their components can cross the gut-blood barrier during disruption, through bloodstreams where bacteria release their metabolites, which cross the BBB and reach the central nervous system. The vagus nerve is composed of enter-endocrine cells (EECs) located on a gut sensory epithelial layer. The EEC has an extending part called a neuropod cell, which connects the gut lumen and the brain stem, allowing for bi-directional signaling. This figure was generated using Biorender.com.

Figure 2

Polarization of microglia and astrocytes and their role in causing neurodegeneration upon microbial infection. This figure was illustrated using Biorender.com.