To keep commensal microbes in check and fight off infections, our immune system relies heavily on helper T cells. In the Parkinson’s video, we refer to these cells as “Signals operators” (Sigs), because they don’t kill microbes directly themselves—helper T cells detect microbes and then call-up other immune cells to do the killing for them.
Their pivotal role became apparent in the 1980s, with the emergence of the AIDS epidemic. The HIV virus causes AIDS by gradually killing helper T cells over a period of about a decade (see figure below). Humans usually have ~1000 helper T cells per microliter of blood. As this count drops, AIDS patients become more susceptible to infections and to overgrowth of microbes which are normally present in humans. The first clinical signs of AIDS are typically overgrowth of commensal fungi, because helper T cells play a crucial role in detecting and controlling fungi. These fungi include Candida in the mouth (Coleman 1993), Malassezia on the skin (Berger 1988), and Pneumocystis in the lungs (Selik 1988).
In the early 1980s, it was not yet realized that nearly all human lungs are asymptomatically colonized by Pneumocystis: the AIDS epidemic revealed their presence because pneumonia caused by this fungus develops when helper T cells are no longer doing a good job at keeping Pneumocystis in check (Ponce 2010).
Similarly, it was not known until 2018 that Malassezia colonize our internal organs in addition to colonizing our skin. Malassezia overgrowth inside the body might explain many idiopathic AIDS symptoms. One of these symptoms is AIDS-associated parkinsonism, where dopaminergic neurons in the brain are dying at an unusually fast rate (Reyes 1991; Sardar 1996). This is very similar to sporadic Parkinson’s disease: symptoms are nearly identical, but progression is more rapid, and young individuals are affected—a rarity in sporadic Parkinson’s disease.
Interestingly, sporadic Parkinson’s patients have lower helper T cells counts as compared to age-matched controls (Bas 2001, Baba 2005, Stevens 2012, Niwa 2012, Saunders 2012, Kustrimovic 2016). This reduction in helper T cells is quite similar to what is observed in the first years of AIDS. This means sporadic Parkinson’s patients are somewhat immunocompromised—but not because of HIV/AIDS.
AIDS-induced parkinsonism and the low helper T cell counts seen in sporadic Parkinson’s disease suggest that helper T cells are protecting dopaminergic neurons in the brain from an infection. This means Parkinson’s disease might be prevented by helping our immune system fight-off causative microbes. In the next posts we’ll look at the different lines of evidence suggesting the culprits may be the usual suspects, Malassezia.
This post was mainly based on Laurence 2019.
Animated Parkinson’s video: https://youtu.be/NEusgOerL5U
