New insights into immune responses to malaria

Date:
July 23, 2021
Source:
Walter and Eliza Hall Institute
Summary:
Advanced technologies have been used to solve a long-standing
mystery about why some people develop serious illness when they
are infected with the malaria parasite, while others carry the
infection asymptomatically.



FULL STORY ========================================================================== Advanced technologies have been used to solve a long-standing mystery
about why some people develop serious illness when they are infected with
the malaria parasite, while others carry the infection asymptomatically.


==========================================================================
An international team used mass cytometry -- an in-depth way of
characterising individual cells -- and machine learning to discover
'immune signatures' associated with symptomatic or asymptomatic infections
in people infected with the Plasmodium vivax parasite. This uncovered
an unexpected role for immune T cells in protection against malaria,
a finding that could help to improve the development of much-needed
malaria vaccines.

The research, which was published in the journal JCI Insight was led
by WEHI's Dr Lisa Ioannidis and Associate Professor Diana Hansen, in collaboration with Professor Ric Price from the Menzies School of Health Research, Darwin, and Dr Rintis Noviyanti from the Eijkman Institute
for Molecular Biology, Indonesia.

Variable immune responses Malaria is a parasitic disease impacting
hundreds of millions of people each year. After infection, people
develop immunity to the Plasmodium parasite that causes malaria -- but
this immunity only reduces the disease severity rather than preventing infection altogether. Despite the immense global impact of malaria,
there are not yet vaccines in clinical use to prevent this disease.

The immune response to malaria is a 'double-edged sword', Associate
Professor Hansen said. "While an immune response to the parasite can
prevent severe disease, in some people it is an excessive immune response
-- driving severe inflammation -- that exacerbates malaria, causing the
most severe, and potentially fatal, symptoms," she said.



==========================================================================
"Our research has investigated the longstanding question of how immune responses differ between people with symptomatic and asymptomatic malaria infections. We focussed on the Plasmodium vivax form of malaria, which
is most common in the Asia-Pacific and Latin America. This species is
a particular challenge to control as infected people can carry it for
many months in the liver without symptoms." Using the University of Melbourne's mass cytometry facility, the research team were able to
undertake in-depth, multi-dimensional assessments of the immune cells
in blood samples provided by people living in a vivax malaria-endemic
region of Indonesia. Dr Ioannidis said the team compared many aspects
of immunity in samples from people who were uninfected, asymptomatically infected, or symptomatically infected with P. vivax.

"In collaboration with a WEHI bioinformatics team led by Professor Gordon Smyth, we used machine learning to develop an 'immune signature' that distinguised between these three categories of samples. These signatures
could be applied to new blood samples from people infected with malaria,
to accurately predict the severity of their infection," Dr Ioannidis said.

Enhancing malaria control Dr Ioannidis said the immune signatures
revealed the key components of the immune response that drive immunity to malaria. "Antibodies produced by B cells were one important component, especially in people with high parasite loads and symptomatic disease,
but we also discovered that certain types of CD4 T cells were critical
to keep infections in check, preventing symptoms," she said.

"This is the first time CD4 T cells have been shown to be important
for controlling asymptomatic P. vivax infections." Associate Professor
Hansen said the discovery could lead to better approaches to controlling
-- or even eliminating -- malaria. "Malaria vaccine development has
focussed almost entirely on measuring antibody responses as a marker of
vaccine success. Our research has revealed the important role of CD4
T cells in controlling malaria infections -- and we think these cells
need much more consideration when designing malaria vaccines. Because
vivax malaria can persist in asymptomatic people, it is critical that
vaccines activate CD4 T cells to control these low-grade infections,"
Associate Professor Hansen said.

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


========================================================================== Journal Reference:
1. Lisa J. Ioannidis, Halina M. Pietrzak, Ann Ly, Retno A.S. Utami,
Emily M.

Eriksson, Stephanie I. Studniberg, Waruni Abeysekera,
Connie S.N. Li-Wai- Suen, Dylan Sheerin, Julie Healer,
Agatha M. Puspitasari, Dwi Apriyanti, Farah N. Coutrier, Jeanne
R. Poespoprodjo, Enny Kenangalem, Benediktus Andries, Pak Prayoga,
Novita Sariyanti, Gordon K. Smyth, Leily Trianty, Alan F. Cowman,
Ric N. Price, Rintis Noviyanti, Diana S. Hansen. High- dimensional
mass cytometry identifies T cell and B cell signatures predicting
reduced risk of Plasmodium vivax malaria. JCI Insight, 2021; 6
(14) DOI: 10.1172/jci.insight.148086 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210723105256.htm

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