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Age-Related Differential Stimulation of Immune Response by Babesia microti and Borrelia burgdorferi During Acute Phase of Infection Affects Disease Severity.
Front Immunol. 2018; 9:2891.FI

Abstract

Lyme disease is the most prominent tick-borne disease with 300,000 cases estimated by CDC every year while ~2,000 cases of babesiosis occur per year in the United States. Simultaneous infection with Babesia microti and Borrelia burgdorferi are now the most common tick-transmitted coinfections in the U.S.A., and they are a serious health problem because coinfected patients show more intense and persisting disease symptoms. B. burgdorferi is an extracellular spirochete responsible for systemic Lyme disease while B. microti is a protozoan that infects erythrocytes and causes babesiosis. Immune status and spleen health are important for resolution of babesiosis, which is more severe and even fatal in the elderly and splenectomized patients. Therefore, we investigated the effect of each pathogen on host immune response and consequently on severity of disease manifestations in both young, and 30 weeks old C3H mice. At the acute stage of infection, Th1 polarization in young mice spleen was associated with increased IFN-γ and TNF-α producing T cells and a high Tregs/Th17 ratio. Together, these changes could help in the resolution of both infections in young mice and also prevent fatality by B. microti infection as observed with WA-1 strain of Babesia. In older mature mice, Th2 polarization at acute phase of B. burgdorferi infection could play a more effective role in preventing Lyme disease symptoms. As a result, enhanced B. burgdorferi survival and increased tissue colonization results in severe Lyme arthritis only in young coinfected mice. At 3 weeks post-infection, diminished pathogen-specific antibody production in coinfected young, but not older mice, as compared to mice infected with each pathogen individually may also contribute to increased inflammation observed due to B. burgdorferi infection, thus causing persistent Lyme disease observed in coinfected mice and reported in patients. Thus, higher combined proinflammatory response to B. burgdorferi due to Th1 and Th17 cells likely reduced B. microti parasitemia significantly only in young mice later in infection, while the presence of B. microti reduced humoral immunity later in infection and enhanced tissue colonization by Lyme spirochetes in these mice even at the acute stage, thereby increasing inflammatory arthritis.

Authors+Show Affiliations

Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, United States.Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, United States.Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, United States.Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, United States.Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30619263

Citation

Djokic, Vitomir, et al. "Age-Related Differential Stimulation of Immune Response By Babesia Microti and Borrelia Burgdorferi During Acute Phase of Infection Affects Disease Severity." Frontiers in Immunology, vol. 9, 2018, p. 2891.
Djokic V, Primus S, Akoolo L, et al. Age-Related Differential Stimulation of Immune Response by Babesia microti and Borrelia burgdorferi During Acute Phase of Infection Affects Disease Severity. Front Immunol. 2018;9:2891.
Djokic, V., Primus, S., Akoolo, L., Chakraborti, M., & Parveen, N. (2018). Age-Related Differential Stimulation of Immune Response by Babesia microti and Borrelia burgdorferi During Acute Phase of Infection Affects Disease Severity. Frontiers in Immunology, 9, 2891. https://doi.org/10.3389/fimmu.2018.02891
Djokic V, et al. Age-Related Differential Stimulation of Immune Response By Babesia Microti and Borrelia Burgdorferi During Acute Phase of Infection Affects Disease Severity. Front Immunol. 2018;9:2891. PubMed PMID: 30619263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-Related Differential Stimulation of Immune Response by Babesia microti and Borrelia burgdorferi During Acute Phase of Infection Affects Disease Severity. AU - Djokic,Vitomir, AU - Primus,Shekerah, AU - Akoolo,Lavoisier, AU - Chakraborti,Monideep, AU - Parveen,Nikhat, Y1 - 2018/12/07/ PY - 2018/08/14/received PY - 2018/11/26/accepted PY - 2019/1/9/entrez PY - 2019/1/9/pubmed PY - 2019/10/28/medline KW - Babesia microti KW - Borrelia burgdorferi KW - Lyme disease KW - age-related immunity KW - babesiosis KW - immunity to tick-borne coinfections SP - 2891 EP - 2891 JF - Frontiers in immunology JO - Front Immunol VL - 9 N2 - Lyme disease is the most prominent tick-borne disease with 300,000 cases estimated by CDC every year while ~2,000 cases of babesiosis occur per year in the United States. Simultaneous infection with Babesia microti and Borrelia burgdorferi are now the most common tick-transmitted coinfections in the U.S.A., and they are a serious health problem because coinfected patients show more intense and persisting disease symptoms. B. burgdorferi is an extracellular spirochete responsible for systemic Lyme disease while B. microti is a protozoan that infects erythrocytes and causes babesiosis. Immune status and spleen health are important for resolution of babesiosis, which is more severe and even fatal in the elderly and splenectomized patients. Therefore, we investigated the effect of each pathogen on host immune response and consequently on severity of disease manifestations in both young, and 30 weeks old C3H mice. At the acute stage of infection, Th1 polarization in young mice spleen was associated with increased IFN-γ and TNF-α producing T cells and a high Tregs/Th17 ratio. Together, these changes could help in the resolution of both infections in young mice and also prevent fatality by B. microti infection as observed with WA-1 strain of Babesia. In older mature mice, Th2 polarization at acute phase of B. burgdorferi infection could play a more effective role in preventing Lyme disease symptoms. As a result, enhanced B. burgdorferi survival and increased tissue colonization results in severe Lyme arthritis only in young coinfected mice. At 3 weeks post-infection, diminished pathogen-specific antibody production in coinfected young, but not older mice, as compared to mice infected with each pathogen individually may also contribute to increased inflammation observed due to B. burgdorferi infection, thus causing persistent Lyme disease observed in coinfected mice and reported in patients. Thus, higher combined proinflammatory response to B. burgdorferi due to Th1 and Th17 cells likely reduced B. microti parasitemia significantly only in young mice later in infection, while the presence of B. microti reduced humoral immunity later in infection and enhanced tissue colonization by Lyme spirochetes in these mice even at the acute stage, thereby increasing inflammatory arthritis. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/30619263/Age_Related_Differential_Stimulation_of_Immune_Response_by_Babesia_microti_and_Borrelia_burgdorferi_During_Acute_Phase_of_Infection_Affects_Disease_Severity_ L2 - https://doi.org/10.3389/fimmu.2018.02891 DB - PRIME DP - Unbound Medicine ER -