Michael W. Russell, PhD.

After researching a potential treatment for gonorrhea based on modifying immune response, Michael Russell, PhD, urges scientists to attack infections in new ways.

‘Think Like Pathogens’ to Fight Infection

Published June 10, 2015

In the fight against infectious disease, University at Buffalo immunologist Michael W. Russell, PhD, professor of microbiology and immunology, advocates a novel alternative to antibiotics and vaccines: directly target the immune system.

“Our immune system is extraordinarily capable and adaptable. It is amenable to exploitation to enhance protective immunity against a potentially unlimited variety of pathogens. ”
Michael W. Russell, PhD
Professor of microbiology and immunology

“We can do this by tweaking it in some way to generate effective immune responses,” Russell writes in his opinion piece in mBio.

Such interventions, he notes, come with a significant advantage: “they should sidestep the problem of antibiotic resistance.”

A New Approach: Exploit Immune System

Russell is not suggesting that researchers forgo the quest for better antibiotics or conventional or novel types of vaccines. “These options must be vigorously pursued,” he says.

But he supports adding novel approaches to the infection-fighting arsenal.

He advocates for “interventions that rely on the ability of the adaptive immune system to mount a seemingly limitless array of defenses against pathogens.”

“Our immune system is extraordinarily capable and adaptable,” Russell asserts. “It is amenable to exploitation to enhance protective immunity against a potentially unlimited variety of pathogens.”

Counter-Manipulating Pathogens

Science should no longer view microbial pathogenicity as a “simple linear process” between the pathogen, which attacks, and the host, which defends, Russell argues.

“Pathogens manipulate the host immune response to favor their own survival or exploit inherent weaknesses in the immune system,” he explains. 

“By better understanding the methods pathogens use to constantly stay one step ahead of immune defenses, scientists can learn to ‘counter-manipulate’ how they subvert the immune response, and thereby induce effective immunity,” Russell adds.

Recent research has revealed that both pathogen and host have sensory mechanisms that quickly detect the presence of the other. “The outcome may be an emergent property of the interaction between host and pathogen, not easily predictable from separate consideration of their characteristics,” he writes.

Complex, Ingenious Host-Pathogen Interactions

Russell’s research on gonococcal infection has enhanced understanding of what he calls “the complex and ingenious interactions between hosts and pathogens.”

He and his colleagues developed the concept that gonococcal infection seems to inhibit specific adaptive immune responses. This explains, in part, why people can become infected multiple times. 

“It turns out that gonococcal infection very cleverly controls the immune system. It induces responses the Neisseria gonorrhoeae bacterium can fight, while suppressing the responses it cannot fight,” he says.

In 2013, Russell published a paper describing a potential new treatment for gonorrhea that modifies the immune response to the infection. He based the idea on a cancer treatment a colleague developed that helps stimulate an immune response against tumors.

In preclinical studies, the potential treatment reversed the infection’s suppression of the immune response. It also offered protection against future reinfections in animals, establishing “immune memory.”

“This approach of tweaking the immune system should work well against mucosal surface infections in the mouth, genital tract and gastrointestinal and respiratory systems — where the great majority of infectious diseases first invade the body,” he says.

He cautions that much more research is needed to demonstrate these advantages.

Addressing Growing Health Threats

Successful interventions that harness the power of the immune system would help alleviate pressing health concerns.

“Amid the emergence of so-called ‘superbugs,’ antibiotic resistance threatens to render some infections untreatable,” Russell notes.

Fewer drugs are effective against some viruses and eukaryotic pathogens, he writes, “most notably in the case of malaria, where resistance to artemisinin appeared sooner than anticipated.”

The World Health Organization estimates more than 100 million cases of gonorrhea occur each year and warns of a pending crisis due to soaring resistance to current treatments. The Centers for Disease Control cited N. gonorrhoeae as one of the top three pathogens requiring urgent action.

“Scientists must develop a better understanding of the human immune system and its adaptability in order to take full advantage of it,” Russell concludes.

His mBio Opinion/Hypothesis article is titled “Thinking Globally, Acting Locally: Harnessing the Immune System to Deal with Recalcitrant Pathogens.”