Spectrin-based skeleton in red blood cells and malaria

Dhermy, Didier; Schrével, Joseph; Lecomte, Marie‐Christine

doi:10.1097/moh.0b013e3280d21afd

Cited by 42 publications

(30 citation statements)

References 28 publications

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“…Another example of how A. phagocytophilum alters the cytoskeleton is through actin phosphorylation to selectively regulate gene transcription in association with RNA polymerase II (RNAPII) and the TATA-binding protein in ticks (18). Interestingly, certain spectrin mutations or polymorphisms have been shown to constitute new factors of innate resistance to malaria in vitro (43).…”

Section: Discussionmentioning

confidence: 99%

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

et al. 2013

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dAnaplasma phagocytophilum causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects gene expression in both the vertebrate host and the tick vector, Ixodes scapularis. Here, we identified new genes, including spectrin alpha chain or alpha-fodrin (CG8) and voltage-dependent anion-selective channel or mitochondrial porin (T2), that are involved in A. phagocytophilum infection/multiplication and the tick cell response to infection. The pathogen downregulated the expression of CG8 in tick salivary glands and T2 in both the gut and salivary glands to inhibit apoptosis as a mechanism to subvert host cell defenses and increase infection. In the gut, the tick response to infection through CG8 upregulation was used by the pathogen to increase infection due to the cytoskeleton rearrangement that is required for pathogen infection. These results increase our understanding of the role of tick genes during A. phagocytophilum infection and multiplication and demonstrate that the pathogen uses similar strategies to establish infection in both vertebrate and invertebrate hosts.T icks are ectoparasites of animals and humans and are considered to be the most important arthropod vector of pathogens in some regions (1). Ixodes scapularis Say (Acari: Ixodidae) is an important vector of pathogens that infect and cause disease in humans and domestic animals in the United States. Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), the focus of this study, is the causative agent of human, canine, and equine granulocytic anaplasmosis and tick-borne fever of ruminants (2, 3).A. phagocytophilum is an intracellular bacterium that infects vertebrate host neutrophils, where it multiplies within a parasitophorous vacuole, thus evading host defenses while inhibiting apoptosis and promoting cytoskeleton rearrangement for infection and multiplication (4-8). Tick-A. phagocytophilum interactions are not as well characterized as those between pathogen and vertebrate hosts (4). While A. phagocytophilum has been shown to infect I. scapularis gut cells (9) and salivary glands (10), the developmental cycle of this pathogen has not been described in ticks. Tick proteins such as Salp16, subolesin, antifreeze glycoprotein IAFGP, and alpha1-3-fucosyltransferease were differentially regulated and required for A. phagocytophilum infection of I. scapularis (10-20). Activation of heat shock proteins and other stress response proteins in ticks and cultured tick cells in response to A. phagocytophilum infection was also characterized by proteomics and transcriptomics analyses (21).The overall goal of our research is to characterize molecular interactions at the vector-pathogen interface and develop vaccines for the control of tick infestations and pathogen infection/transmission. Our hypothesis is that tick genes differentially expressed in response to pathogen infection would include those involved in pathogen infection, multiplication, and transmission, as well as in the tick protective response to infection. In this researc...

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Section: Discussionmentioning

confidence: 99%

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

et al. 2013

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“…It is much more common in areas of endemic malaria, particularly in people of African and Mediterranean ancestry, presumably because elliptocytes confer some resistance to malaria. 51 The world-wide incidence of HE has been estimated to be 1 in 2000 to 4000 individuals with the incidence of HE approaching 1 in 100 in parts of Africa. 50, 52 The true incidence of HE is unknown, as many affected patients are asymptomatic.…”

Section: Introductionmentioning

confidence: 99%

Abnormalities of the Erythrocyte Membrane

Gallagher

2013

Pediatric Clinics of North America

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Synopsis Primary abnormalities of the erythrocyte membrane, including the hereditary spherocytosis and hereditary elliptocytosis syndromes, are an important group of inherited hemolytic anemias. Classified by distinctive morphology on peripheral blood smear, these disorders are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Once considered routine, growing recognition of the longterm risks of splenectomy, including cardiovascular disease, thrombotic disorders, and pulmonary hypertension, as well as the emergence of penicillin-resistant pneumococci, a concern for infection in overwhelming postsplenectomy infection, have led to re-evaluation of the role of splenectomy. Current management guidelines acknowledge these important considerations when entertaining splenectomy and recommend detailed discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy.

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“…84 HE has a worldwide distribution, but is more common in malaria endemic regions with prevalence approaching 2% in West Africa. 85 Inheritance of HE is autosomal dominant. The overwhelming majority of HE is asymptomatic but approximately 10% of patients have moderate to severe anemia including a few reported cases of hydrops fetalis.…”

Section: Mechanistic Basis For Altered Membrane and Cell Function In mentioning

confidence: 99%