PARTNERS IN CRIME

Two strains of the malarial parasite cooperate with 
each other to counter the host's defences, says Biplab Das

The tenacity of the malarial parasite makes it one of man's most dangerous enemies. Medical scientists are familiar with its ability to evade the host's immune system. Now, researchers have found that two different coexisting strains of the parasite can adopt a cooperative strategy against the host's defences. 

The research team, comprising Adrian Hill of Oxford University and his colleagues from the UK Medical Research Council Laboratories in Fajara, The Gambia, and the London School of Hygiene and Tropical Medicine, discovered this while studying sections of the Gambian population.

The finding, reported in a recent issue of Science, provides researchers an opportunity to study the molecular arms race between Plasmodium falciparum and the host. Shortly after entering bloodstream, the parasite encounters a huge array of immune responses. Hill's team focused on the initial attack launched by the host's immune system. 

Initially, the parasites migrate to the host's liver cells. Here, they invite host's human leukocyte antigens (HLA), which bind to small fragments of proteins from the parasites. Subsequently, immune cells called cytotoxic T lymphocytes (CTSs) latch onto HLA-bound fragments to kill the parasites. 

Despite this system of defence, some of the parasites escape. These are the ones, which are helping Hill and his colleagues to decipher the molecular details of the clinical CTL response.

HLA-B35, a kind of HLA, is common in the Gambian population. HLA-B35 binds to a specific circumsporozoite protein of  plasmodium falciparum. This combination provokes CTLs to attack the parasite. Among the four variants of the parasite's circumsporozoite proteins, two of them (cp26 and cp22) bind with HLA-B35. 

In lab studies, Hill's team found that CTLs could not kill the two coexisting strains of the parasite simultaneously. This was because the proteins of one of the two strains block the release of CTLs, which could destroy the other strain. 

However, the question remained whether this mutual understanding between the two strains works in patients. For the answer, the team studied malarial parasite DNA taken from 800 patients. Analysing strains, they found the variants, which survived the initial attack in the liver. 

More than 40 per cent of the patients were carrying more than one strain of the parasite. "We found a much higher co-occurrence of the two strains containing cp26 and cp29," says Hill. Their cooperative strategy seemed to help them survive the host's immune attack. The team also found the presence of HLA-B35 with two circumsporozoite proteins - cp26 and cp29. 

With knowledge about the specific functions of different human leukocyte antigens, scientists could tilt the balance in the host's favour.