A new understanding of how the immune system deals with malaria

Date:
April 19, 2022
Source:
Karolinska Institutet
Summary:
By analysing samples from patients who have been treated for
malaria in Sweden, researchers can now describe how the immune
system acts to protect the body after a malaria infection. The
results provide knowledge that can aid in the development of more
effective vaccines against the disease.



FULL STORY ==========================================================================
By analysing samples from patients who have been treated for malaria in
Sweden, researchers at Karolinska Institutet can now describe how the
immune system acts to protect the body after a malaria infection. The
results, published in the journal Cell Reports, provide knowledge that
can aid in the development of more effective vaccines against the disease.


==========================================================================
"Our results contribute to a better understanding of how humans fight this serious disease and may help in the development of better vaccines," says Christopher Sundling, principal researcher at the Department of Medicine, Solna, at Karolinska Institutet, and last author of the study. "This
sheds new light on the question of how the body's immunse system deals
with malaria." Malaria is caused by parasites that are spread to humans
by mosquitoes. The disease caused more than 600,000 deaths in 2020,
mainly among young children in sub-Saharan Africa.

People who contract malaria repeatedly may gradually become immune to
the disease. But even before that, the body can build up a so-called
tolerance, which provides protection against severe disease.

To find out more about how disease tolerance develops, KI researchers have investigated immune cells and proteins in blood samples from patients who
have been treated for acute malaria infection at Karolinska University
Hospital in Solna, Sweden and have recovered.

This patient group was monitored by being tested on six occasions during
one year following the onset of the disease. A total of 53 patients
were included, 17 of whom had contracted malaria for the first time,
while 36 had grown up in malaria endemic areas, had had malaria many
times before and now contracted the disease again after travel.



========================================================================== "Since we have followed the patients here in Sweden, we can study the
natural course of the immune response after a malaria infection, without
the risk of a new infection interfering with the results. This cohort
has proved to be very valuable for studying the immunology of malaria,"
says Anna Fa"rnert, Professor of Infectious Diseases at the Department
of Medicine, Solna, Karolinska Institutet and Senior infectious diseases physician at Karolinska University Hospital, Sweden in whose research
group the study was conducted.

Within this cohort, the researchers recently described the kinetics of
antibody responses after infection.

In the case of malaria, the disease itself is partly a result of the inflammation created in the body by the immune system's reaction to
the infection. In their comparisons, the researchers noted a strong inflammatory response from the so-called innate immune system in people
who were infected for the first time. In contrast, the people who were re-infected had an ability to suppress the inflammation, Christopher
Sundling explains.

"In those who have had malaria before, we saw that the early presence
of parasite-specific antibodies interrupt the first stages of the
inflammation and prevent a certain type of inflammatory T-cell from
expanding," Sundling continues.

In October 2021, the World Health Organization recommended the use
of the world's first, and so far, only vaccine against malaria,
Mosquirix. However, Mosquirix targets only one form of the malaria
parasite -- the form the parasite has when it first moves from the
mosquito into the liver. Once it enters the bloodstream and gives
symptoms, the pathogen is at a different stage against which the vaccine
does not work.

"This is a weakness of the current vaccine. Understanding how tolerance develops and what happens in the blood stage can help us develop other
types of vaccines, which may not fully protect against infection but
will lessen the chances of becoming seriously ill. If such a vaccine
can enable people to survive the first infections that kill so many,
we could save many lives," says Sundling.

Over the last decades, the incidence of malaria decreased
globally. Efforts to distribute mosquito nets, spray insecticides indoors,
as well as diagnostics and new treatments are believed to have contributed
to the positive trend, Anna Fa"rnert notes. But in recent years, the rate
of decline has levelled off and in 2020 the covid pandemic contributed
to increased mortality.

"We now need to continue to ensure that people are protected from being
bitten by infected mosquitoes and have access to rapid and effective
treatment. But to further reduce the burden of disease and eventually
eradicate malaria, new tools are required. An effective vaccine is really needed; that is how we have been able to manage other infections, also
in poor countries," says Anna Fa"rnert.

The research has been funded by the Swedish Research Council, Magnus
Bergvall Foundation, the AAke Wiberg Foundation, Region Stockholm,
and the Marianne and Marcus Wallenberg Foundation, as well as doctoral
grants from Karolinska Institutet.


========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Maximilian Julius Lautenbach, Victor Yman, Carolina Sousa Silva,
Nadir
Kadri, Ioanna Broumou, Sherwin Chan, Sina Angenendt, Klara Sonde'n,
David Fernando Plaza, Anna Fa"rnert, Christopher Sundling. Systems
analysis shows a role of cytophilic antibodies in shaping innate
tolerance to malaria. Cell Reports, 2022; 39 (3): 110709 DOI:
10.1016/ j.celrep.2022.110709 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220419112516.htm

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