Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease.

Woelsung Yi; Weili Bao; Marilis Rodriguez; Yunfeng Liu; Manpreet Singh; Vijendra Ramlall; Jeny R Cursino-Santos; Hui Zhong; Catherine M Elton; Gavin J Wright; Avital Mendelson; Xiuli An; Cheryl A Lobo; Karina Yazdanbakhsh

doi:10.1182/bloodadvances.2018026468

Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease.

Woelsung Yi, Weili Bao, Marilis Rodriguez, Yunfeng Liu, Manpreet Singh, Vijendra Ramlall, Jeny R Cursino-Santos, Hui Zhong, Catherine M Elton, Gavin J Wright, Avital Mendelson, Xiuli An, Cheryl A Lobo, Karina Yazdanbakhsh

Research output: Contribution to journal › Article › peer-review

Abstract

The intraerythrocytic parasite Babesia microti is the number 1 cause of transfusion-transmitted infection and can induce serious, often life-threatening complications in immunocompromised individuals including transfusion-dependent patients with sickle cell disease (SCD). Despite the existence of strong long-lasting immunological protection against a second infection in mouse models, little is known about the cell types or the kinetics of protective adaptive immunity mounted following Babesia infection, especially in infection-prone SCD that are thought to have an impaired immune system. Here, we show, using a mouse B microti infection model, that infected wild-type (WT) mice mount a very strong adaptive immune response, characterized by (1) coordinated induction of a robust germinal center (GC) reaction; (2) development of follicular helper T (TFH) cells that comprise ∼30% of splenic CD4+ T cells at peak expansion by 10 days postinfection; and (3) high levels of effector T-cell cytokines, including interleukin 21 and interferon γ, with an increase in the secretion of antigen (Ag)-specific antibodies (Abs). Strikingly, the Townes SCD mouse model had significantly lower levels of parasitemia. Despite a highly disorganized splenic architecture before infection, these mice elicited a surprisingly robust adaptive immune response (including comparable levels of GC B cells, TFH cells, and effector cytokines as control and sickle trait mice), but higher immunoglobulin G responses against 2 Babesia-specific proteins, which may contain potential immunogenic epitopes. Together, these studies establish the robust emergence of adaptive immunity to Babesia even in immunologically compromised SCD mice. Identification of potentially immunogenic epitopes has implications to identify long-term carriers, and aid Ag-specific vaccine development. © 2018 by The American Society of Hematology.

Original language	English
Pages (from-to)	3462-3478
Number of pages	17
Journal	Blood Advances
Volume	2
Issue number	23
DOIs	https://doi.org/10.1182/bloodadvances.2018026468
Publication status	Published - 11 Dec 2018

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© 2018 by The American Society of Hematology. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details
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Yi, W., Bao, W., Rodriguez, M., Liu, Y., Singh, M., Ramlall, V., Cursino-Santos, J. R., Zhong, H., Elton, C. M., Wright, G. J., Mendelson, A., An, X., Lobo, C. A., & Yazdanbakhsh, K. (2018). Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease. Blood Advances, 2(23), 3462-3478. https://doi.org/10.1182/bloodadvances.2018026468

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title = "Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease.",

abstract = "The intraerythrocytic parasite Babesia microti is the number 1 cause of transfusion-transmitted infection and can induce serious, often life-threatening complications in immunocompromised individuals including transfusion-dependent patients with sickle cell disease (SCD). Despite the existence of strong long-lasting immunological protection against a second infection in mouse models, little is known about the cell types or the kinetics of protective adaptive immunity mounted following Babesia infection, especially in infection-prone SCD that are thought to have an impaired immune system. Here, we show, using a mouse B microti infection model, that infected wild-type (WT) mice mount a very strong adaptive immune response, characterized by (1) coordinated induction of a robust germinal center (GC) reaction; (2) development of follicular helper T (TFH) cells that comprise ∼30% of splenic CD4+ T cells at peak expansion by 10 days postinfection; and (3) high levels of effector T-cell cytokines, including interleukin 21 and interferon γ, with an increase in the secretion of antigen (Ag)-specific antibodies (Abs). Strikingly, the Townes SCD mouse model had significantly lower levels of parasitemia. Despite a highly disorganized splenic architecture before infection, these mice elicited a surprisingly robust adaptive immune response (including comparable levels of GC B cells, TFH cells, and effector cytokines as control and sickle trait mice), but higher immunoglobulin G responses against 2 Babesia-specific proteins, which may contain potential immunogenic epitopes. Together, these studies establish the robust emergence of adaptive immunity to Babesia even in immunologically compromised SCD mice. Identification of potentially immunogenic epitopes has implications to identify long-term carriers, and aid Ag-specific vaccine development. {\textcopyright} 2018 by The American Society of Hematology.",

author = "Woelsung Yi and Weili Bao and Marilis Rodriguez and Yunfeng Liu and Manpreet Singh and Vijendra Ramlall and Cursino-Santos, {Jeny R} and Hui Zhong and Elton, {Catherine M} and Wright, {Gavin J} and Avital Mendelson and Xiuli An and Lobo, {Cheryl A} and Karina Yazdanbakhsh",

note = "{\textcopyright} 2018 by The American Society of Hematology. Uploaded in accordance with the publisher{\textquoteright}s self-archiving policy. Further copying may not be permitted; contact the publisher for details",

year = "2018",

month = dec,

day = "11",

doi = "10.1182/bloodadvances.2018026468",

language = "English",

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Yi, W, Bao, W, Rodriguez, M, Liu, Y, Singh, M, Ramlall, V, Cursino-Santos, JR, Zhong, H, Elton, CM, Wright, GJ, Mendelson, A, An, X, Lobo, CA & Yazdanbakhsh, K 2018, 'Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease.', Blood Advances, vol. 2, no. 23, pp. 3462-3478. https://doi.org/10.1182/bloodadvances.2018026468

TY - JOUR

T1 - Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease.

AU - Yi, Woelsung

AU - Bao, Weili

AU - Rodriguez, Marilis

AU - Liu, Yunfeng

AU - Singh, Manpreet

AU - Ramlall, Vijendra

AU - Cursino-Santos, Jeny R

AU - Zhong, Hui

AU - Elton, Catherine M

AU - Wright, Gavin J

AU - Mendelson, Avital

AU - An, Xiuli

AU - Lobo, Cheryl A

AU - Yazdanbakhsh, Karina

PY - 2018/12/11

Y1 - 2018/12/11

N2 - The intraerythrocytic parasite Babesia microti is the number 1 cause of transfusion-transmitted infection and can induce serious, often life-threatening complications in immunocompromised individuals including transfusion-dependent patients with sickle cell disease (SCD). Despite the existence of strong long-lasting immunological protection against a second infection in mouse models, little is known about the cell types or the kinetics of protective adaptive immunity mounted following Babesia infection, especially in infection-prone SCD that are thought to have an impaired immune system. Here, we show, using a mouse B microti infection model, that infected wild-type (WT) mice mount a very strong adaptive immune response, characterized by (1) coordinated induction of a robust germinal center (GC) reaction; (2) development of follicular helper T (TFH) cells that comprise ∼30% of splenic CD4+ T cells at peak expansion by 10 days postinfection; and (3) high levels of effector T-cell cytokines, including interleukin 21 and interferon γ, with an increase in the secretion of antigen (Ag)-specific antibodies (Abs). Strikingly, the Townes SCD mouse model had significantly lower levels of parasitemia. Despite a highly disorganized splenic architecture before infection, these mice elicited a surprisingly robust adaptive immune response (including comparable levels of GC B cells, TFH cells, and effector cytokines as control and sickle trait mice), but higher immunoglobulin G responses against 2 Babesia-specific proteins, which may contain potential immunogenic epitopes. Together, these studies establish the robust emergence of adaptive immunity to Babesia even in immunologically compromised SCD mice. Identification of potentially immunogenic epitopes has implications to identify long-term carriers, and aid Ag-specific vaccine development. © 2018 by The American Society of Hematology.

AB - The intraerythrocytic parasite Babesia microti is the number 1 cause of transfusion-transmitted infection and can induce serious, often life-threatening complications in immunocompromised individuals including transfusion-dependent patients with sickle cell disease (SCD). Despite the existence of strong long-lasting immunological protection against a second infection in mouse models, little is known about the cell types or the kinetics of protective adaptive immunity mounted following Babesia infection, especially in infection-prone SCD that are thought to have an impaired immune system. Here, we show, using a mouse B microti infection model, that infected wild-type (WT) mice mount a very strong adaptive immune response, characterized by (1) coordinated induction of a robust germinal center (GC) reaction; (2) development of follicular helper T (TFH) cells that comprise ∼30% of splenic CD4+ T cells at peak expansion by 10 days postinfection; and (3) high levels of effector T-cell cytokines, including interleukin 21 and interferon γ, with an increase in the secretion of antigen (Ag)-specific antibodies (Abs). Strikingly, the Townes SCD mouse model had significantly lower levels of parasitemia. Despite a highly disorganized splenic architecture before infection, these mice elicited a surprisingly robust adaptive immune response (including comparable levels of GC B cells, TFH cells, and effector cytokines as control and sickle trait mice), but higher immunoglobulin G responses against 2 Babesia-specific proteins, which may contain potential immunogenic epitopes. Together, these studies establish the robust emergence of adaptive immunity to Babesia even in immunologically compromised SCD mice. Identification of potentially immunogenic epitopes has implications to identify long-term carriers, and aid Ag-specific vaccine development. © 2018 by The American Society of Hematology.

U2 - 10.1182/bloodadvances.2018026468

DO - 10.1182/bloodadvances.2018026468

M3 - Article

VL - 2

SP - 3462

EP - 3478

JO - Blood Advances

JF - Blood Advances

SN - 2473-9529

IS - 23

ER -