AUTHOR=Lakkavaram Asha L. , Maymand Saeed , Naser Wasan , Ward Alister C. , de Koning-Ward Tania F. 

TITLE=Cish knockout mice exhibit similar outcomes to malaria infection despite altered hematopoietic responses

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1288876

DOI=10.3389/fmicb.2023.1288876

ISSN=1664-302X

ABSTRACT=<p>The Cytokine-inducible Src homology 2 domain-containing (CISH) protein is a negative feedback regulator induced by cytokines that play key roles in immunity and erythropoiesis. Single nucleotide polymorphisms (SNPs) in the human <italic>CISH</italic> gene have been associated with increased susceptibility to severe malaria disease. To directly assess how CISH might influence outcomes in the BALB/c model of malaria anemia, CISH knockout (<italic>Cish</italic><sup>−/−</sup>) mice on this background were infected with <italic>Plasmodium berghei</italic> and their hematopoietic responses, cytokine production and ability to succumb to severe malaria disease evaluated. Despite basal erythrocytic disruption, upon <italic>P. berghei</italic> infection, the <italic>Cish <sup>−/−</sup></italic> mice were better able to maintain peripheral blood cell counts, hemoglobin levels and a steady-state pattern of erythroid differentiation compared to wild-type (<italic>Cish</italic><sup>+/+</sup>) mice. Ablation of CISH, however, did not influence the outcome of acute malaria infections in either the BALB/c model or the alternative C57BL/6 model of experimental cerebral malaria, with the kinetics of infection, parasite load, weight loss and cytokine responses being similar between <italic>Cish</italic><sup>+/+</sup> and <italic>Cish<sup>−/−</sup></italic> mice, and both genotypes succumbed to experimental cerebral malaria within a comparable timeframe.</p>