Agustín Rolandelli

University of Maryland, Baltimore

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Joaquín Miguel Pellegrini

Aix-Marseille Université

Domingo Palmero

Hospital Muñiz

Verónica García

University of Buenos Aires

Joao H. F. Pedra

University of Maryland, Baltimore

Nancy Liliana Tateosian

Consejo Nacional de Investigaciones Científicas y Técnicas

Nicolás Oscar Amiano

Fundación Ciencias Exactas y Naturales

Anya J. O’Neal

Memorial Sloan Kettering Cancer Center

L. Rainer Butler

University of Maryland, Baltimore

Sourabh Samaddar

Bose Institute

Hanna J. Laukaitis-Yousey

University of Maryland, Baltimore

Cooperative Institutions

University of Maryland, Baltimore

Consejo Nacional de Investigaciones Científicas y Técnicas

Yale University

University of Buenos Aires

Fundación Ciencias Exactas y Naturales

University of Baltimore

Hospital Muñiz

University of New Haven

Howard Hughes Medical Institute

University of Maryland, College Park

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Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection

Nature Microbiology (2024)

Sourabh Samaddar Agustín Rolandelli Anya J. O’Neal Hanna J. Laukaitis-Yousey Liron Marnin

Ixodes scapularis

Anaplasma phagocytophilum

Obligate

Amblyomma americanum

10.1038/s41564-024-01756-0

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Citations (4)

Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Liron Marnin Luisa M. Valencia Haikel N. Bogale Hanna J. Laukaitis-Yousey Agustín Rolandelli

Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to hematophagy and arthropod-borne diseases. Hematophagous ectoparasites, including ticks, subvert the wound healing response to maintain prolonged attachment and facilitate blood-feeding. Here, we unveil a strategy by which extracellular vesicles (EVs) ensure blood-feeding and arthropod survival in three medically relevant tick species. We demonstrate through single cell RNA sequencing and murine genetics that wildtype animals infested with EV-deficient

Homeostasis

Extracellular Vesicles

10.1101/2023.11.10.566612

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Citations (2)

Lipid hijacking: A unifying theme in vector-borne diseases

eLife (2020)

Anya J. O’Neal L. Rainer Butler Agustín Rolandelli Stacey D. Gilk Joao H. F. Pedra

Vector-borne illnesses comprise a significant portion of human maladies, representing 17% of global infections. Transmission of vector-borne pathogens to mammals primarily occurs by hematophagous arthropods. It is speculated that blood may provide a unique environment that aids in the replication and pathogenesis of these microbes. Lipids and their derivatives are one component enriched in blood and are essential for microbial survival. For instance, the malarial parasite Plasmodium falciparum and the Lyme disease spirochete Borrelia burgdorferi , among others, have been shown to scavenge and manipulate host lipids for structural support, metabolism, replication, immune evasion, and disease severity. In this Review , we will explore the importance of lipid hijacking for the growth and persistence of these microbes in both mammalian hosts and arthropod vectors.

Plasmodium (life cycle)

10.7554/elife.61675

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Citations (57)

IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease

Autophagy (2017)

Nancy Liliana Tateosian Joaquín Miguel Pellegrini Nicolás Oscar Amiano Agustín Rolandelli Nicolás Casco

During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen.

10.1080/15548627.2017.1320636

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Citations (41)

Genetic manipulation of anIxodes scapulariscell line

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Neeta Singh Agustín Rolandelli Anya J. O’Neal L. Rainer Butler Sourabh Samaddar

Abstract Although genetic manipulation is one of the hallmarks in model organisms, its applicability to non-model species has remained difficult due to our limited understanding of their fundamental biology. For instance, manipulation of a cell line originated from the blacklegged tick Ixodes scapularis, an arthropod that serves as a vector of several human pathogens, has yet to be established. Here, we demonstrate the successful genetic modification of the commonly used tick ISE6 line through ectopic expression and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing. We performed ectopic expression using nucleofection and attained CRISPR-Cas9 editing via homology dependent recombination. Targeting the E3 ubiquitin ligase X-linked inhibitor of apoptosis ( xiap ) and its substrate p47 led to alteration in molecular signaling within the immune deficiency (IMD) network and increased infection of the rickettsial agent Anaplasma phagocytophilum in I. scapularis ISE6 cells. Collectively, our findings complement techniques for genetic engineering of ticks in vivo and aid in circumventing the long-life cycle of I. scapularis, of which limits efficient and scalable molecular genetic screens. Importance Genetic engineering in arachnids has lagged compared to insects, largely because of substantial differences in their biology. This study unveils the implementation of ectopic expression and CRISPR-Cas9 gene editing in a tick cell line. We introduced fluorescently tagged proteins in ISE6 cells and edited its genome via homology dependent recombination. We ablated the expression of xiap and p47 , two signaling molecules present in the immune deficiency (IMD) pathway of I. scapularis . Impairment of the tick IMD pathway, an analogous network of the tumor necrosis factor receptor in mammals, led to enhanced infection of the rickettsial agent A. phagocytophilum . Altogether, our findings provide a critical technical resource to the scientific community to enable a deeper understanding of biological circuits in the blacklegged tick Ixodes scapularis .

Ixodes scapularis

10.1101/2023.09.08.556855

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Citations (3)

Genetic manipulation of an Ixodes scapularis cell line

mBio (2024)

Neeta Singh Agustín Rolandelli Anya J. O’Neal L. Rainer Butler Sourabh Samaddar

Although genetic manipulation is one of the hallmarks of model organisms, its applicability to non-model species has remained difficult due to our limited understanding of their fundamental biology. For instance, manipulation of a cell line originated from the black-legged tick

Ixodes scapularis

Line (geometry)

10.1128/mbio.02479-23

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Citations (3)

Author Correction: PGE2 displays immunosuppressive effects during human active tuberculosis

Scientific Reports (2021)

Joaquín Miguel Pellegrini Candela Martin María Paula Morelli Julieta Aylén Schander Nancy Liliana Tateosian

10.1038/s41598-021-97720-7

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Citations (1)

Tick hemocytes have pleiotropic roles in microbial infection and arthropod fitness

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Agustín Rolandelli Hanna J. Laukaitis-Yousey Haikel N. Bogale Nisha Singh Sourabh Samaddar

Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here, we describe immune cells or hemocytes from the clinically relevant tick

Arthropod

10.1101/2023.08.31.555785

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Citations (3)

Circulating Monocyte-Like Myeloid Derived Suppressor Cells and CD16 Positive Monocytes Correlate With Immunological Responsiveness of Tuberculosis Patients

Frontiers in Cellular and Infection Microbiology (2022)

Nicolás Oscar Amiano Joaquín Miguel Pellegrini María Paula Morelli Camila Martinena Agustín Rolandelli

Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis ( Mtb -Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb -Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations.

CD16

Monocyte

Myeloid-derived Suppressor Cell

10.3389/fcimb.2022.841741

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Citations (8)

CD36 homologs determine microbial resistance to the Lyme disease spirochete

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Anya J. O’Neal Nisha Singh Iain S. Forrest Agustín Rolandelli Xiaowei Wang

Abstract Pattern recognition receptors sense pathogens in arthropods and mammals through distinct immune processes. Whether these molecules share a similar function and recognize the same microbe in evolutionarily distant species remain ill-defined. Here, we establish that the CD36 superfamily is required for Borrelia burgdorferi resistance in both the arthropod vector and humans. Using the blacklegged tick Ixodes scapularis and an electronic health record-linked biobank, we demonstrate that CD36 members elicit immunity to the Lyme disease spirochete. In ticks, the CD36-like protein Croquemort recognizes lipids and initiates the immune deficiency and jun N-terminal kinase pathways against B. burgdorferi . In humans, exome sequencing and clinical information reveal that individuals with CD36 loss-of-function variants have increased prevalence of Lyme disease. Altogether, we discovered a conserved mechanism of anti-bacterial immunity. One Sentence Summary Lipid receptors belonging to the CD36 superfamily exhibit a shared immune function in both ticks and humans.

Ixodes scapularis

10.1101/2022.02.09.479763

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Citations (0)