Rickettsial pathogen inhibits tick cell death through tryptophan metabolite mediated activation of p38 MAP kinase

Namjoshi, Prachi; Dahmani, Mustapha; Sultana, Hameeda; Neelakanta, Girish

doi:10.1016/j.isci.2022.105730

Cited by 4 publications

(5 citation statements)

References 57 publications

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“…The results from ELISA, immunoblotting and immunofluorescence analyses that show increased levels of IsOATP4056 in A. phagocytophilum -infected ticks and tick cells compared to the levels noted in uninfected controls are in line with the gene expression data previously published from our laboratory 35 , 37 , 38 , 46 . Based on the primary amino acid sequence, the expected molecular weight of the protein is approximately 100 kDa.…”

Section: Discussionsupporting

confidence: 89%

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Immunization against arthropod protein impairs transmission of rickettsial pathogen from ticks to the vertebrate host

et al. 2023

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Human anaplasmosis caused by Anaplasma phagocytophilum is one of the most common tick-borne diseases in the United States. The black-legged ticks, Ixodes scapularis, vector and transmit this bacterium to humans. In this study, we provide evidence that targeting I. scapularis membrane-bound organic anion transporting polypeptide 4056 (IsOATP4056) with an anti-vector vaccine affects transmission of A. phagocytophilum from ticks to the vertebrate host. Anaplasma phagocytophilum induces expression of IsOATP4056 in ticks and tick cells. Increased membrane localization of IsOATP4056 was evident in A. phagocytophilum-infected tick cells. Treatment with high dose (10 µg/ml) but not low dose (5 µg/ml) of EL-6 antibody that targets the largest extracellular loop of IsOATP4056 showed cytotoxic effects in tick cells but not in human keratinocyte cell line (HaCaT). Passive immunization, tick-mediated transmission and in vitro studies performed with mice ordered from two commercial vendors and with tick cells showed that EL-6 antibody not only impairs A. phagocytophilum transmission from ticks to the murine host but also aids in the reduction in the bacterial loads within engorged ticks and in tick cells by activation of arthropod Toll pathway. Furthermore, reduced molting efficiency was noted in ticks fed on EL-6 antibody-immunized mice. Collectively, these results provide a good candidate for the development of anti-tick vaccine to target the transmission of A. phagocytophilum and perhaps other tick-borne pathogens of medical importance.

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Section: Discussionsupporting

confidence: 89%

“…Live/Dead and MTT assays were performed as described in our previous publications 46 , 52 . Briefly, 3 × 10 4 tick cells were plated in each well of a 96 well plate (Griener Bio One, ThermoFisherScientific, USA).…”

Section: Methodsmentioning

confidence: 99%

Immunization against arthropod protein impairs transmission of rickettsial pathogen from ticks to the vertebrate host

et al. 2023

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“…RNAi interference is a widely used technique in addressing the role of tick genes in blood feeding and pathogen interactions [16,17,20,35,[41][42][43][44][45][46][47][48][49][50]. Our study provided evidence for the use of an in vitro feeding system to knockdown gene expression in O. turicata americanus ticks.…”

Section: Discussionmentioning

confidence: 67%

“…The sequence alignment and phylogenetic analysis was performed as described [ 43 ]. The following are the GenBank Accession numbers for Toll sequences: KAG0432202.1- Ixodes persulcatus , KAH6927628.1- Hyalomma asiaticum , XP_029821922.2- Ixodes scapularis , XP_037282253.1- Rhipicephalus microplus , XP_037520387.1- Rhipicephalus sanguineus , XP_037577366.1- Dermacentor silvarum , XP_050026248.1- Dermacentor andersoni .…”

Section: Methodsmentioning

confidence: 99%

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Anti-tick vaccine candidate subolesin is important for blood feeding and innate immune gene expression in soft ticks

Nandy,

Tamakloe,

Sonenshine

et al. 2023

PLoS Negl Trop Dis

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Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme precursor (Lp), fibrinogen-domain containing protein (FDP), cystatin and ML-domain containing protein (MLD) in O. turicata americanus ticks. Quantitative real-time polymerase chain reaction analysis revealed the expression of these genes in both O. turicata americanus salivary glands and midgut and in all developmental stages of these soft ticks. Significantly increased expression of fdp was noted in salivary glands and midgut upon O. turicata americanus blood feeding. Furthermore, RNAi-mediated knockdown of O. turicata americanus subolesin expression affected blood feeding and innate immune gene expression in these ticks. Significant downregulation of toll, lp, fdp, cystatin, and mld transcripts was evident in sub-dsRNA-treated ticks when compared to the levels noted in mock-dsRNA-treated control. Collectively, our study not only reports identification and characterization of various innate immune genes in O. turicata americanus ticks but also provides evidence on the role of subolesin in blood feeding and innate immune gene expression in these medically important ticks.

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Antibody-blocking of a tick transporter impairs Anaplasma phagocytophilum colonization in Haemaphysalis longicornis ticks

Namjoshi,

Lubembe,

Sultana

et al. 2024

Sci Rep

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The invasive Asian longhorned tick Haemaphysalis longicornis that vectors and transmits several animal pathogens is significantly expanding in the United States. Recent studies report that these ticks also harbor human pathogens including Borrelia burgdorferi sensu lato, Babesia microti, and Anaplasma phagocytophilum. Therefore, studies that address the interactions of these ticks with human pathogens are important. In this study, we report the characterization of H. longicornis organic anion-transporting polypeptides (OATPs) in interactions of these ticks with A. phagocytophilum. Using OATP-signature sequence, we identified six OATPs in the H. longicornis genome. Bioinformatic analysis revealed that H. longicornis OATPs are closer to other tick orthologs rather than to mammalian counterparts. Quantitative real-time PCR analysis revealed that OATPs are highly expressed in immature stages when compared to mature stages of these ticks. In addition, we noted that the presence of A. phagocytophilum upregulates a specific OATP in these ticks. We also noted that exogenous treatment of H. longicornis with xanthurenic acid, a tryptophan metabolite, influenced OATP expression in these ticks. Immunoblotting analysis revealed that antibody generated against Ixodes scapularis OATP cross-reacted with H. longicornis OATP. Furthermore, treatment of H. longicornis with OATP antibody impaired colonization of A. phagocytophilum in these ticks. These results not only provide evidence that the OATP-tryptophan pathway is important for A. phagocytophilum survival in H. longicornis ticks but also indicate OATP as a promising candidate for the development of a universal anti-tick vaccine to target this bacterium and perhaps other rickettsial pathogens of medical importance.

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Rickettsial pathogen inhibits tick cell death through tryptophan metabolite mediated activation of p38 MAP kinase

Cited by 4 publications

References 57 publications

Immunization against arthropod protein impairs transmission of rickettsial pathogen from ticks to the vertebrate host

Immunization against arthropod protein impairs transmission of rickettsial pathogen from ticks to the vertebrate host

Anti-tick vaccine candidate subolesin is important for blood feeding and innate immune gene expression in soft ticks

Antibody-blocking of a tick transporter impairs Anaplasma phagocytophilum colonization in Haemaphysalis longicornis ticks

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