In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 10 ( 2023-10-9), p. e1011679-
Abstract:
Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor ( Tfrc Y20H/Y20H ), which limits the ability of cells to internalise iron from plasma. At homeostasis Tfrc Y20H/Y20H mice appear healthy and are not anaemic. However, Tfrc Y20H/Y20H mice infected with Plasmodium chabaudi chabaudi AS showed significantly higher peak parasitaemia and body weight loss. We found that Tfrc Y20H/Y20H mice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead, P . chabaudi infected Tfrc Y20H/Y20H mice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as ex vivo iron supplementation fully recovered CD4 + T cell and B cell function. Despite the inhibited immune response and increased parasitaemia, Tfrc Y20H/Y20H mice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011679
DOI:
10.1371/journal.ppat.1011679.g001
DOI:
10.1371/journal.ppat.1011679.g002
DOI:
10.1371/journal.ppat.1011679.g003
DOI:
10.1371/journal.ppat.1011679.g004
DOI:
10.1371/journal.ppat.1011679.g005
DOI:
10.1371/journal.ppat.1011679.g006
DOI:
10.1371/journal.ppat.1011679.g007
DOI:
10.1371/journal.ppat.1011679.t001
DOI:
10.1371/journal.ppat.1011679.s001
DOI:
10.1371/journal.ppat.1011679.s002
DOI:
10.1371/journal.ppat.1011679.s003
DOI:
10.1371/journal.ppat.1011679.s004
DOI:
10.1371/journal.ppat.1011679.s005
DOI:
10.1371/journal.ppat.1011679.s006
DOI:
10.1371/journal.ppat.1011679.r001
DOI:
10.1371/journal.ppat.1011679.r002
DOI:
10.1371/journal.ppat.1011679.r003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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