The contribution of Natural Killer Complex loci to the development of experimental cerebral malaria

Hansen, Diana S., Ryg-Cornejo, Victoria, Ioannidis, Lisa J., Chiu, Chris Y., Ly, Ann, Nie, Catherine Q., Scalzo, Anthony A., and Schofield, Louis (2014) The contribution of Natural Killer Complex loci to the development of experimental cerebral malaria. PLoS ONE, 9 (4). e93268. pp. 1-8.

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Abstract

Background: The Natural Killer Complex (NKC) is a genetic region of highly linked genes encoding several receptors involved in the control of NK cell function. The NKC is highly polymorphic and allelic variability of various NKC loci has been demonstrated in inbred mice, providing evidence for NKC haplotypes. Using BALB.B6-Cmv1(r) congenic mice, in which NKC genes from C57BL/6 mice were introduced into the BALB/c background, we have previously shown that the NKC is a genetic determinant of malarial pathogenesis. C57BL/6 alleles are associated with increased disease-susceptibility as BALB.B6-Cmv1(r) congenic mice had increased cerebral pathology and death rates during P. berghei ANKA infection than cerebral malaria-resistant BALB/c controls.

Methods: To investigate which regions of the NKC are involved in susceptibility to experimental cerebral malaria (ECM), intra-NKC congenic mice generated by backcrossing recombinant F2 progeny from a (BALB/c x BALB.B6-Cmv1(r)) F1 intercross to BALB/c mice were infected with P. berghei ANKA.

Results: Our results revealed that C57BL/6 alleles at two locations in the NKC contribute to the development of ECM. The increased severity to severe disease in intra-NKC congenic mice was not associated with higher parasite burdens but correlated with a significantly enhanced systemic IFN-gamma response to infection and an increased recruitment of CD8(+) T cells to the brain of infected animals.

Conclusions: Polymorphisms within the NKC modulate malarial pathogenesis and acquired immune responses to infection.

Item ID: 35422
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

© 2014 Hansen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: Victorian State Government, National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC IRIISS Grant, NHMRC Project Grant 1031212
Date Deposited: 24 Sep 2014 07:12
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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