Helminths and Susceptibility to HIV?????????? A Medical Mystery Waiting to be Solved

A couple of times over the last year, I have described early stage research into the potential of helminths to prevent cancer?  File this post under the same heading:  the very beginning of a new area of research.

Sometimes it just hits me how much we don’t know. Today is one of those days.

The idea exists in the medical community that helminth colonization is associated with a greater risk of infection with HIV.  Certainly, the parts of the world where colonization with helminths is still the norm (the non-industrialized world) have much higher rates of HIV/AIDS.  And prior research shows, as just one example, that Schistosoma mansoni (SM), a kind of fluke common in the non-industrialized world, “… has been linked with an increased risk of HIV acquisition in women…. [In women uninfected with HIV] Schistosomiasis treatment induces a profound reduction of HIV entry into cervical and blood CD4+ T cells that is sustained for up to two months.”[i]

Many times over the years I have written about helminths (intestinal worms, which are the major component of the human macrobiome (which we have eradicated in the industrialized world)) so my regular readers are familiar with their remarkable immune modulating capabilities.  For those less familiar:  in order to survive in you, helminths modulate the immune system and inflammatory response. One of their main benefits is that they boost levels of regulatory cytokines, which modulate inflammation. They also modulate the activity of a kind of immune cell called CD4+ which is a kind of T-lymphocyte…which also happens to be the main  immune cell affected by HIV.

So logically, it makes perfect sense that the reduction of inflammation in the body predisposes us toward a greater likelihood of acute infection from viruses (like HIV) and bacteria.  After all, inflammation is our bodies’ natural response to fight infection.

HOWEVER…

“… many areas endemic for S. mansoni infection have high HIV-1 prevalence rates, indicating that co-infection is likely. However, clear epidemiological evidence to date is lacking for the assumption that treating S. mansoni in co-infected individuals would be beneficial for their HIV-1 disease, as studies have reported contradictory findings.”[ii]

And now, research just published in PLOS Pathogens has determined, through in vitro experimentation, that helminths  appear to reduce human susceptibility to HIV infection.[iii]

Researchers from Liverpool and Amsterdam found that an extract from the eggs of this same helminth, S. mansoni, blocked HIV transmission.  They discovered that the mechanism of action involves the binding of a component of the extract to dendritic (immune) cells, which ordinarily promote HIV infection.  In binding to the dendritic cells this way, the extract of the helminth eggs “…reduced the susceptibility of T-cells to HIV-1 infection.”  A second component of the helminth egg extract was also found to modulate HIV infection.

Of course this needs a huge amount of further testing.  There are so many factors that still have to be determined, including what kind of helminth eggs may work (or is it only the eggs of S. mansoni)? Can only the extract prevent or alleviate infection or can the egg from the live worm also work in vivo?  If the latter, what kind of helminth load would be necessary to be efficacious? Is this preparation a potential anti-HIV treatment?  And what about other viruses?  Do helminths or their eggs have anti-viral properties, in general?

In spite of the many questions still to be answered, this is still a pretty astounding finding:  “We provide evidence here that Th cells…are less susceptible to R5 HIV-1 infection, suggesting that helminthic infections may be beneficial when considering HIV-1.”

In 2015, researchers at Duke University’s School of Medicine  and the University of North Carolina at Chapel Hill published a paper that examined the effects on the immune system of lab rats when their macrobiomes were restored. Prior research had demonstrated that “…low levels of ‘natural’ antibodies were found in laboratory rats compared to wild rats. This finding has implications for the progression of cancer in biome depleted environments, since natural antibodies are important for tumor surveillance.”[iv]  Biome enrichment in helminths led to an enhanced immune responsiveness (increased humoral immunity, meaning better production of antibodies) as opposed to a decrease that you might expect:

“These studies suggest that biome depletion [i.e. the loss of the helminths of our macrobiome] may be associated with attenuated humoral immune responses…To the extent that biome depletion affects laboratory animals and humans in Western countries in a similar fashion, the implications of this finding are potentially far-reaching.  For example, attenuated responses to tumor antigens as a result of biome depletion might underlie, at least in part, the proposed connection between increased rates of cancer and biome depletion.”

And of course, decreased humoral immunity, as a result of biome depletion, suggests that we are less able to mount appropriate antibody responses to viral infections.

????????

Where this leaves us – I have no idea.  Science has yet to come up with any kind of definitive answer.  We’re catching this line of research right at the beginning, I think, so we’ll just have to wait and watch.

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[i] Yegorov, S, et. al. Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways. Nature Communications. 2019;10(2296). doi: 10.1038/s41467-019-09900-9

[ii] https://medicalxpress.com/news/2019-09-helminthic-infections-beneficial-hiv-.html

[iii] Mouser EE, Pollakis G, Smits HH, Thomas J, Yazdanbakhsh M, de Jong EC, et al. (2019) Schistosoma mansoni soluble egg antigen (SEA) and recombinant Omega-1 modulate induced CD4+ T-lymphocyte responses and HIV-1 infection in vitro. PLoS Pathog 15(9): e1007924. doi.org/10.1371/journal.ppat.1007924

[iv] Pi, C. et. al. Increased biodiversity in the environment improves the humoral response of rats.  PLOS One. 2015;10(4).  doi:10.1371/journal.pone.0120255.