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

Asha L Lakkavaram; Saeed Maymand; Wasan Naser; Alister C Ward; Tania F de Koning-Ward

doi:10.3389/fmicb.2023.1288876

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

Front Microbiol. 2023 Nov 2:14:1288876. doi: 10.3389/fmicb.2023.1288876. eCollection 2023.

Authors

Asha L Lakkavaram¹, Saeed Maymand¹, Wasan Naser^{1

2}, Alister C Ward^{1

3}, Tania F de Koning-Ward^{1

3}

Affiliations

¹ School of Medicine, Deakin University, Waurn Ponds, VIC, Australia.
² College of Science, University of Baghdad, Baghdad, Iraq.
³ Institute for Mental and Physical Health and Clinical Translation, Geelong, VIC, Australia.

Abstract

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 CISH 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 (Cish^-/-) mice on this background were infected with Plasmodium berghei and their hematopoietic responses, cytokine production and ability to succumb to severe malaria disease evaluated. Despite basal erythrocytic disruption, upon P. berghei infection, the Cish ^-/- mice were better able to maintain peripheral blood cell counts, hemoglobin levels and a steady-state pattern of erythroid differentiation compared to wild-type (Cish^+/+) 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 Cish^+/+ and Cish^-/- mice, and both genotypes succumbed to experimental cerebral malaria within a comparable timeframe.

Keywords: CISH; Plasmodium; anemia; cerebral malaria; erythropoiesis; hematopoiesis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. TdK-W was supported by an NHMRC Senior Research Fellowship (ID 1136300), AL and SM received PhD stipends from Deakin University, and WN received PhD stipend from the Higher Committee for Education (HCED) of Iraq.