"Armadillos are a bit scary," allows dermatologist and immunologist Robert Modlin, who is on the faculty at the University of California at Los Angeles.
"They have big claws," he continued, "and you can get leprosy from inhabitants of Louisiana and Texas. The people who live in those two states often get infected because they are exposed to Mycobacterium leprae, the pathogen of leprosy. Some 40 percent of those inhabitants are naturally infected somehow by M. leprae. The folks there eat them and skin them and bet on them in armadillo races. So I recommend to everybody," Modlin added straight-faced, "to have their nine-banded armadillos [Basypus movemcinctus] autoclaved, and not eaten medium rare.
"As a matter of fact, M. leprae is nothing to laugh about," he went on. "It affects the skin, peripheral nerves, upper respiratory tract and eyes. That infection can lead to severe disfigurement of the hands, face and feet. Armadillos are mammals despite their horny appearance, and the only animals that can model for the leprosy pathogen.
"Most of the infection starts in the skin, due to the fact that the human skin has a lower temperature than the rest of the body," he said. "The bacteria can grow readily in the nine-banded armadillo, which has a body temperature of 70 degrees F. Leprosy patients develop a lack of sensation in their typical nerve deficits. They're unable to differentiate sharp from dull, sour from sweet, or hot from cold. So threatened leprous fingers and toes get no attention, and waste away."
Modlin is senior author of an article in Science dated Sept. 12, 2003. Its title: "Use of genetic profiling in leprosy to discriminate clinical forms of the disease."
"I think there are two major findings in this Science paper," Modlin observed. "The first is that you can use gene expression profiling to distinguish different forms of leprosy. The importance of this is that it should be possible to use the technology to help diagnose and classify patients with leprous microbial infection, [and] eventually to predict the onset of complications, so that intervention by appropriate therapy can occur early.
"It should be possible some day to go into your doctor's office," Modlin foresaw, "and from a drop of blood be able to tell whether you were suffering from a common cold or been exposed to deadly anthrax. So I think this is what the message is in terms of the utility of gene expression profiling in clinical medicine."
LIR-7, Toll Receptors Come Into Their Own
"Our second finding area," Modlin volunteered, "is what one learns about leprosy. Here we've been able to discover something new, which is that the family of receptors, known as LIR - leukocyte immunoglobulin-like receptors - were associated with the progressive form of the infection. Our paper showed that one of them, LIR-7, could be triggered to set off an anti-inflammatory response. That blocks the Toll-like receptor pathway, which leads to the production of immune-system cytokines.
"Toll-like receptors form part of the sensors of our innate immune systems that have the ability to recognize biochemical patterns of different microbes. Toll, too, is an antimicrobial pathway, so in that manner it would have the ability to down-regulate cell-mediated immunity. This is not appropriate in the context of an intracellular infection, such as Mycobacteria leprae. But it could be a useful therapeutic in the treatment of autoimmune diseases, where such an inflammatory response leads to destruction of host tissues. So that's the second thing we've learned: identifying a novel anti-inflammatory pathway.
"The pathogen itself is an intercellular bacterium," he noted. "One of the first hemopathogens was identified in 1874 by Gerhard Hansen (1841-1912), a Norwegian physician who gave leprosy his name as Hansen's disease.' It's one of the few pathogens that cannot be grown in the laboratory, so it has to be cultured in the nine-banded armadillo. Its liver is harvested so the bacteria can be isolated and various parts of its structure purified. It's a very slow-growing bacterium," Modlin pointed out, "with a long incubation period of several years. According to the Guinness Book of World Records, it's the least contagious pathogen. That's because in the most endemic areas the incidence of leprosy is extremely low and most people who are exposed don't develop the disease. Only a small portion do. And you can't just travel to an endemic country for a weekend and catch leprosy; you have to live there for a number of months.
"Leprosy exists in two persuasions: mild and self-curing, severe and life-threatening. Those are the poles of its pathogenic spectrum of clinical manifestations," Modlin continued. "It correlates to the level of the immune system's response to the bacteria. And so in this paper we've studied the patients with the most disseminated progressive form, known as lepromatous leprosy. And the patients with the most limited form are tuberculoid. At one end of the spectrum, the tuberculoid form [T-lep] is characterized by limited disease with few bacteria and local expression of Type 1 cytokines, characteristic of strong cell-mediated immunity. In contrast, lepromatous leprosy [L-lep] patients present clinically with widespread lesions and high bacterial loads."
Group Files Patent Antibody Claim
"What we want to do now is try to understand whether we can predict if leprosy sufferers are going to have complications where we can intervene to prevent the nerve damage, which is very devastating," he said. "We'd also like to further research the role of LIR-7 to understand which cell types it's on, how it's contributing to immune suppression in leprosy and how it's blocking LIR-7 or using LIR-7 activation to treat leprosy and other diseases - such as TB, leishmaniasis, or malaria."
Modlin calls the attention of readers to a small footnote reference toward the end of the Science paper. It reads: "The percentage of LIR-7+ peripheral blood monocytes were similar in normal donors. We were not able to obtain the antibody against LIR-7 from Amgen Inc. for tissue labeling because the parties have been unable to agree to a mutually acceptable material transfer agreement."
"We've just filed a patent application to protect our invention," Modlin disclosed, "the first evidence that LIR-7 has the anti-inflammatory properties. That's what we're claiming," he concluded.