Autoimmune hemolytic anemia associated with babesiosis

Narurkar, Roshni; Mamorska-Dyga, Aleksandra; Nelson, John; Liu, Delong

doi:10.1186/s40364-017-0095-6

Cited by 28 publications

(16 citation statements)

References 32 publications

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“…It is postulated that the rupture of the plasmatic membrane of the erythrocyte is potentially accompanied by the release of hemoglobin during the course of the egress process. This may explain the hemolysis and hemoglobinuria in babesiosis ( Zintl et al., 2003 ; Gray et al., 2010 ; Hildebrandt et al., 2013 ; Narurkar et al., 2017 ).…”

Section: Discussionmentioning

confidence: 98%

The Cross-Species Immunity During Acute Babesia Co-Infection in Mice

Zafar

Galon

Kondoh

et al. 2022

Front. Cell. Infect. Microbiol.

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Babesiosis causes high morbidity and mortality in immunocompromised individuals. An earlier study suggested that lethal Babesia rodhaini infection in murine can be evaded by Babesia microti primary infection via activated macrophage-based immune response during the chronic stage of infection. However, whether the same immune dynamics occur during acute B. microti co-infection is not known. Hence, we used the mouse model to investigate the host immunity during simultaneous acute disease caused by two Babesia species of different pathogenicity. Results showed that B. microti primary infection attenuated parasitemia and conferred immunity in challenge-infected mice as early as day 4 post-primary infection. Likewise, acute Babesia co-infection undermined the splenic immune response, characterized by the significant decrease in splenic B and T cells leading to the reduction in antibody levels and decline in humoral immunity. Interestingly, increased macrophage and natural killer splenic cell populations were observed, depicting their subtle role in the protection. Pro-inflammatory cytokines (i.e. IFN-γ, TNF-α) were downregulated, while the anti-inflammatory cytokine IL-10 was upregulated in mouse sera during the acute phase of Babesia co-infection. Herein, the major cytokines implicated in the lethality caused by B. rodhaini infection were IFN- γ and IL-10. Surprisingly, significant differences in the levels of serum IFN- γ and IL-10 between co-infected survival groups (day 4 and 6 challenge) indicated that even a two-day delay in challenge infection was crucial for the resulting pathology. Additionally, oxidative stress in the form of reactive oxygen species contributed to the severity of pathology during acute babesiosis. Histopathological examination of the spleen showed that the erosion of the marginal zone was more pronounced during B. rodhaini infection, while the loss of cellularity of the marginal zone was less evident during co-infection. Future research warrants investigation of the roles of various immune cell subtypes in the mechanism involved in the protection of Babesia co-infected hosts.

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Section: Discussionmentioning

confidence: 98%

The Cross-Species Immunity During Acute Babesia Co-Infection in Mice

Zafar

Galon

Kondoh

et al. 2022

Front. Cell. Infect. Microbiol.

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“…treatment and clinical outcome on follow-up. Of 13 cases reported, seven cases were collected from single case reports; there was one case series including six cases from a single institution [ 10 - 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…AIHA is associated with certain infections, including HIV and malaria [ 9 ]. There have been sporadic cases and one case series reported of immune hemolysis complicating babesiosis in patients with ongoing parasitemia [ 10 - 13 ]. It is unclear if certain host factors may be associated with development of autoantibodies.…”

Section: Introductionmentioning

confidence: 99%

Autoimmune Hemolytic Anemia Associated With Human Babesiosis

Rajapakse

Bakirhan

2021

J Hematol

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“…Intravascular hemolysis occurs in a number of pathologies ranging from genetic hemoglobinopathies [1][2][3] to more acute conditions such as sepsis 4 , pre-eclampsia 5,6 , parasitic infection 7,8 , or in patients after cardiac surgery 9,10 . It is well established that patients with chronic hemolysis, such as in sickle cell disease, are at significantly greater risk for thrombotic complications 11,12 as well as endothelial dysfunction 13,14 and chronic vasculopathy [15][16][17] which lead to morbidities such as stroke 18,19 and pulmonary hypertension (PH) [20][21][22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

Heme stimulates platelet mitochondrial oxidant production via the activation of toll-like receptor 4 signaling to mediate targeted granule secretion

Annarapu

Nolfi‐Donegan

Reynolds

et al. 2021

Preprint

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Hemolysis is a pathological component of many diseases and is associated with thrombosis and vascular dysfunction. Hemolytic products, including cell-free hemoglobin and free heme directly activate platelets. However, the effect of hemolysis on platelet degranulation, a central process in not only thrombosis, but also inflammatory and mitogenic signaling, remains less clear. Our group showed that hemoglobin-induced platelet activation involved the production of mitochondrial reactive oxygen species (mtROS). However, the molecular mechanism by which extracellular hemolysis induces platelet mtROS production, and whether the mtROS regulate platelet degranulation remains unknown. Here, we demonstrate using isolated human platelets that cell free heme is a more potent agonist for platelet activation than hemoglobin, and stimulates the release of a specific set of molecules from the α-granule of platelets, including the glycoprotein thrombospondin-1 (TSP-1). We uncover the mechanism of heme-mediated platelet mtROS production which is dependent on the activation of platelet TLR4 signaling and leads to the downstream phosphorylation of complex-V by the serine kinase Akt. Notably, inhibition of platelet TLR4 or Akt, or scavenging mtROS prevents heme-induced granule release in vitro. Further, heme-dependent granule release is significantly attenuated in vivo in mice lacking TLR4 or those treated with the mtROS scavenger MitoTEMPO. These data elucidate a novel mechanism of TLR4-mediated mitochondrial regulation, establish the mechanistic link between hemolysis and platelet degranulation, and begin to define the heme and mtROS-dependent platelet secretome. These data have implications for hemolysis-induced thrombo-inflammatory signaling and for the consideration of platelet mitochondria as a therapeutic target in hemolytic disorders.

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Autoimmune hemolytic anemia associated with babesiosis

Cited by 28 publications

References 32 publications

The Cross-Species Immunity During Acute Babesia Co-Infection in Mice

The Cross-Species Immunity During Acute Babesia Co-Infection in Mice

Autoimmune Hemolytic Anemia Associated With Human Babesiosis

Heme stimulates platelet mitochondrial oxidant production via the activation of toll-like receptor 4 signaling to mediate targeted granule secretion

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