Cryptosporidiosis, sometimes called “Crypto”, is a disease of severe diarrhea caused by the protozoan parasite Cryptosporidium.
The disease is endemic worldwide and can spread easily through contaminated food or water—local Wisconsinites might recall the 1993 Milwaukee outbreak that affected more than 400,000 people.
Most people can overcome the illness, but immunocompromised patients can suffer from chronic disease and possibly death.
In new research published in the journal Infection and Immunity, scientists at the Morgridge Institute and UW-Madison found that a unique treatment in immunocompromised hosts activated a different immune response pathway to prevent the parasite from spreading.
This research may offer clues as to how Cryptosporidium affects the host and why immunocompromised people are more susceptible to disease.
Morgridge Postdoctoral Fellow Gina Gallego-Lopez says this research is the first step toward understanding the relationship between parasite and host, and ultimately identifying new therapeutic treatments.
For patients with the disease, there is only one approved drug, Nitazoxanide, and it is not effective for immunocompromised patients.
Another challenge is that there simply isn’t much data for severe cases in immunocompromised patients.
“In many countries we don’t have the real data about how many people are getting infected or dying of cryptosporidiosis,” says Gallego-Lopez. “There are a lot of unknowns.”
Gallego-Lopez co-authored the study with graduate student Carolina Mendoza Cavazos, both working with principal investigator (PI) Laura Knoll at UW-Madison, whose research is centered around Toxoplasma. Knoll and Morgridge Investigator Melissa Skala serve as Gallego-Lopez’s co-PI’s through the Morgridge Postdoctoral Fellow Program. Also contributing to the study was Roberta O’Connor, Gallego-Lopez’s former PI and a Cryptosporidium expert now at the University of Minnesota.
In this study, the researchers treated immunocompromised mice infected with Cryptosporidium with soluble Toxoplasma gondii antigens (STAg). This treatment mimics animals in nature with chronic Toxoplasma infection that are protected from other secondary infections.
The Knoll Lab previously reported on using a STAg solution to effectively reduce infections against influenza virus, Plasmodium (which causes malaria), and Listeria. The researchers hoped they would see a similar outcome with Cryptosporidium—and they did.
The STAg treatment reduced shedding of Cryptosporidium oocysts, the life stage of the parasite that is spread through feces as a contaminant of water or food.
Using RNA sequencing, the team analyzed gene expression changes in both the host and the parasite. They found increased expression of 37 genes—all related to the interferon-type-1 immune response—in mice infected and treated with STAg.
This suggests that despite being immunocompromised, there was a boosted immune response through the interferon type-1 pathway, which could ultimately lead to identifying potential therapeutic targets to control infection.
Gallego-Lopez says that Cryptosporidium infection may also be related to colon cancer, but this relationship is still not well understood.
Infection may be a risk factor to develop colon cancer, like how Heliobacter infections in the stomach can cause gastric cancer. Or perhaps cancer patients are immunocompromised and therefore simply more susceptible to crypto infection.
“I really am curious about the relationship between Cryptosporidium and colon cancer, but my first step is to study the metabolism,” says Gallego-Lopez.
Preliminary data in this study shows that STAg treatment reduced the expression of three genes: lactase, fructose-1-biphosphate, and glucose-6-phosphatase catalytic subunit (g6pc).
“These are related to gluconeogenesis and carbohydrate metabolism,” Gallego-Lopez explains. “So in some way, the parasite is affecting how the host obtains energy.”
Dysregulation of metabolism in cells is a hallmark of cancer, and Gallego-Lopez hopes to investigate these metabolic changes further using optical metabolic imaging, a technique she is learning through the Skala Lab at Morgridge.
I want to dedicate my life to study how these parasites change the metabolism of the hosts. I really love research. That’s my dream job.Gina Gallego-Lopez, Morgridge Postdoctoral Fellow
A native of Colombia, Gallego-Lopez grew up in a tropical area where diseases like Chikungunya and Dengue are prevalent.
“I really liked immunology since I was a child,” she says. “I really wanted to know more about these microorganisims, and how to find solutions for all these diseases.”
After working on malaria vaccine development in Colombia, Gallego-Lopez earned her Ph.D. through the O’Connor Lab at Washington State University where she studied the Babesia parasite and gained experience using molecular biology tools.
She met Knoll at a conference, and the two connected through their work on parasites, ultimately leading to her postdoctoral training with Knoll and Skala at UW-Madison and Morgridge.
“Here I’m learning new methodologies and tools, like optical metabolic imaging, to help me with my goal to discover new treatments for these parasites,” she says.
Gallego-Lopez hopes her postdoctoral work will naturally lead to an academic position where she can start her own research lab with a focus on Toxoplasma and Cryptosporidium.
“I want to dedicate my life to study how these parasites change the metabolism of the hosts,” she says. “I really love research. That’s my dream job.”