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The Role of Host PKCα During Intracellular Cryptosporidium Infection

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Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology

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Abstract

Protein Kinase C-α (PKCα) is a serine/threonine kinase that has recently been associated with increased susceptibility in several enteric infections through regulation of host cell actin cytoskeleton. In the scope of Cryptosporidium infection, changes in PKCα expression and activity have been reported in vitro. Past studies have shown Cryptosporidium requires host cell actin polymerization during infection with the identification of some important mediators, [e.g. c-Src, PI3K, Cdc42, N-WASP, Arp 2/3 complex], however a potential mechanism between PKCα and regulation of actin has not been established. Hence, the aim of this review is to present an overview of the progress made thus far attempting to understand changes in host cell characteristics during Cryptosporidium infection and to propose the role of PKCα during this process. We report on findings in the field using techniques such as immunofluorescent imaging, RNA-seq, and transmission electron microscopy (TEM). Although the data linking PKCα and Cryptosporidium is limited in the field, the mechanism outlined is promising for PKCα as a potential target for treatment of cryptosporidiosis.

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Abbreviations

PKC:

Protein Kinase C

PKCα:

Protein Kinase C alpha-protein

CDPK1:

Calcium-dependent protein kinase 1

PKD3:

Protein Kinase D3

RNA-seq:

(RNA-sequencing

TEM:

Transmission electron microscopy

PRKCA :

Protein Kinase C alpha-gene

BKI:

Bumped-kinase Inhibitors

c-Src:

Proto-oncogene tyrosine-protein kinase Src

PI3K:

Phosphoinositide 3-kinase

Cdc42:

Cell Division Cycle 42

N-WASP:

Neural Wiskott-Aldrich syndrome protein

Arp 2/3:

Actin-related protein 2/3

C. parvum :

Cryptosporidium parvum

C. hominis :

Cryptosporidium hominis

PKCβ:

Protein Kinase C beta

JAK2:

Janus Kinase 2

Chk1/2:

Checkpoint Kinase 1/2

SI:

Small intestinal

PKCε:

Protein Kinase C epsilon

F-actin:

Filamentous actin

GTPase:

Guanosine-5′-triphosphate hydrolase enzyme

GEF:

Guanine nucleotide exchange factor

Aqp1:

Aquaporin 1

Sglt1:

Sodium/Glucose transporter 1

HTT:

Host-targeted therapies

FDA:

Food and drug administration

IEC:

Intestinal epithelial cell

EC50:

Effective concentration of inhibitor that reduced infection by half

IC50:

Inhibitory concentration where enzyme binding is reduced by half

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Compliance with Ethical Standards

Funding

This study was funded by Gates Cryptosporidium Grant #: OPP1160655 and Cryptosporidium Field Studies Grant#: R01AI043596.

Disclosure of Interests

All authors declare they have no conflicts of interest.

Human and animal studies discussed in this paper have been previously published. Informed consent for participation and publication was obtained from all individuals.

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Authors and Affiliations

  1. Department of Medicine: Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, USA

    Sayo McCowin & Chelsea Marie

Authors
  1. Sayo McCowin
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  2. Chelsea Marie
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Corresponding author

Correspondence to Chelsea Marie .

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Editors and Affiliations

  1. Institute Pasteur, Paris, France

    Nancy Guillen

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McCowin, S., Marie, C. (2020). The Role of Host PKCα During Intracellular Cryptosporidium Infection. In: Guillen, N. (eds) Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-44826-4_15

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