<i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin
<i>Anaplasma phagocytophilum,</i> the causative agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular bacterium transmitted by the bite of black-legged ticks, <i>Ixodes scapularis</i>. The main host cells in vertebrates are neutrophils. However, the fir...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/12/12/1965 |
| _version_ | 1827638105249677312 |
|---|---|
| author | Jacob Underwood Cristina Harvey Elizabeth Lohstroh Branden Pierce Cross Chambers Stephanie Guzman Valencia Adela S. Oliva Chávez |
| author_facet | Jacob Underwood Cristina Harvey Elizabeth Lohstroh Branden Pierce Cross Chambers Stephanie Guzman Valencia Adela S. Oliva Chávez |
| author_sort | Jacob Underwood |
| collection | DOAJ |
| description | <i>Anaplasma phagocytophilum,</i> the causative agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular bacterium transmitted by the bite of black-legged ticks, <i>Ixodes scapularis</i>. The main host cells in vertebrates are neutrophils. However, the first site of entry is in the skin during tick feeding. Given that the initial responses within skin are a crucial determinant of disease outcome in vector-borne diseases, we used a non-biased approach to characterize the transcriptional changes that take place at the bite during <i>I. scapularis</i> feeding and <i>A. phagocytophilum</i> transmission. Experimentally infected ticks were allowed to feed for 3 days on C57BL/6J mice to allow bacterial transmission and establishment. Skin biopsies were taken from the attachment site of uninfected ticks and <i>A. phagocytophilum</i>-infected ticks. Skin without ticks (intact skin) was used as baseline. RNA was isolated and sequenced using next-generation sequencing (NGS). The differentially expressed genes were used to identify over-represented pathways by gene ontology (GO) and pathway enrichment (PE). <i>Anaplasma phagocytophilum</i> transmission resulted in the activation of interferon signaling and neutrophil chemotaxis pathways in the skin. Interestingly, it also led to the downregulation of genes encoding extracellular matrix (ECM) components, and upregulation of metalloproteinases, suggesting that <i>A. phagocytophilum</i> delays wound healing responses and may increase vascular permeability at the bite site. |
| first_indexed | 2024-03-09T16:11:55Z |
| format | Article |
| id | doaj.art-5fe4de01354d498a91b55cce0c55a7c2 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T16:11:55Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-5fe4de01354d498a91b55cce0c55a7c22023-11-24T16:11:13ZengMDPI AGLife2075-17292022-11-011212196510.3390/life12121965<i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the SkinJacob Underwood0Cristina Harvey1Elizabeth Lohstroh2Branden Pierce3Cross Chambers4Stephanie Guzman Valencia5Adela S. Oliva Chávez6Department of Entomology, Texas A&M University, College Station, TX 77845, USADepartment of Entomology, Texas A&M University, College Station, TX 77845, USADepartment of Entomology, Texas A&M University, College Station, TX 77845, USADepartment of Entomology, Texas A&M University, College Station, TX 77845, USADepartment of Entomology, Texas A&M University, College Station, TX 77845, USADepartment of Entomology, Texas A&M University, College Station, TX 77845, USADepartment of Entomology, Texas A&M University, College Station, TX 77845, USA<i>Anaplasma phagocytophilum,</i> the causative agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular bacterium transmitted by the bite of black-legged ticks, <i>Ixodes scapularis</i>. The main host cells in vertebrates are neutrophils. However, the first site of entry is in the skin during tick feeding. Given that the initial responses within skin are a crucial determinant of disease outcome in vector-borne diseases, we used a non-biased approach to characterize the transcriptional changes that take place at the bite during <i>I. scapularis</i> feeding and <i>A. phagocytophilum</i> transmission. Experimentally infected ticks were allowed to feed for 3 days on C57BL/6J mice to allow bacterial transmission and establishment. Skin biopsies were taken from the attachment site of uninfected ticks and <i>A. phagocytophilum</i>-infected ticks. Skin without ticks (intact skin) was used as baseline. RNA was isolated and sequenced using next-generation sequencing (NGS). The differentially expressed genes were used to identify over-represented pathways by gene ontology (GO) and pathway enrichment (PE). <i>Anaplasma phagocytophilum</i> transmission resulted in the activation of interferon signaling and neutrophil chemotaxis pathways in the skin. Interestingly, it also led to the downregulation of genes encoding extracellular matrix (ECM) components, and upregulation of metalloproteinases, suggesting that <i>A. phagocytophilum</i> delays wound healing responses and may increase vascular permeability at the bite site.https://www.mdpi.com/2075-1729/12/12/1965transmissionticksinnate immune responsesmetalloproteinasesextracellular matrixneutrophils |
| spellingShingle | Jacob Underwood Cristina Harvey Elizabeth Lohstroh Branden Pierce Cross Chambers Stephanie Guzman Valencia Adela S. Oliva Chávez <i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin Life transmission ticks innate immune responses metalloproteinases extracellular matrix neutrophils |
| title | <i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin |
| title_full | <i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin |
| title_fullStr | <i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin |
| title_full_unstemmed | <i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin |
| title_short | <i>Anaplasma phagocytophilum</i> Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin |
| title_sort | i anaplasma phagocytophilum i transmission activates immune pathways while repressing wound healing in the skin |
| topic | transmission ticks innate immune responses metalloproteinases extracellular matrix neutrophils |
| url | https://www.mdpi.com/2075-1729/12/12/1965 |
| work_keys_str_mv | AT jacobunderwood ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin AT cristinaharvey ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin AT elizabethlohstroh ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin AT brandenpierce ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin AT crosschambers ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin AT stephanieguzmanvalencia ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin AT adelasolivachavez ianaplasmaphagocytophilumitransmissionactivatesimmunepathwayswhilerepressingwoundhealingintheskin |