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      Phagocytosis of Leptospira by leukocytes from mice with different susceptibility to leptospirosis and possible role of chemokines

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          Abstract

          Background

          Leptospirosis is a widespread zoonosis caused by pathogenic prokaryotic microbes of the genus Leptospira. Although there are several reports in the literature, host-pathogen interaction is still poorly understood. The role of chemokine expression is important on the chemotaxis, activation and regulation of immune cells. Recent studies have shown that their expression profiles play an important role on the severity of leptospirosis outcome. We evaluated the phagocytosis of Leptospira by spleens cells from C3H/HeJ, C3H/HePas and BALB/c mouse strains, respectively susceptible, intermediate and resistant to leptospirosis, and by RAW 264.7 macrophages. Besides, we evaluated the effects of CCL2 treatment on the phagocytosis. The cells were incubated with or without CCL2 chemokine, and infected with virulent L. interrogans sv Copenhageni. Cells and culture supernatants were collected for subsequent analysis.

          Results

          The number of leptospires was higher in BALB/c cells, CCL2 pre-treated or only infected groups, when compared to C3H/HeJ and C3H/HePas cells. Indeed, CCL2 activation did not interfere in the phagocytosis of Leptospira. Expression of chemokines CXCL5 and CCL8 levels were significantly inhibited in infected BALB/c cells when compared to the non-infected control.

          Conclusions

          Higher ability to phagocytosis and early modulation of some chemokines correlated with the resistance to leptospirosis disease. Exposure to CCL2 did not interfere on phagocytosis of Leptospira in our experimental conditions, but acted in the modulation of chemokines expression during Leptospira infection.

          Electronic supplementary material

          The online version of this article (10.1186/s12866-018-1371-9) contains supplementary material, which is available to authorized users.

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          Most cited references38

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          Virulence of the zoonotic agent of leptospirosis: still terra incognita?

          Pathogenic leptospires are the bacterial agents of leptospirosis, which is an emerging zoonotic disease that affects both animals and humans worldwide. In this Review, the recent advances in our understanding of the epidemiology, taxonomy, genomics and the molecular basis of virulence in leptospires, and of how these properties contribute to the pathogenesis of leptospirosis, are discussed.
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            Role of chemokines in the pathogenesis of acute lung injury.

            Acute lung injury (ALI) is due to an uncontrolled systemic inflammatory response resulting from direct injury to the lung or indirect injury in the setting of a systemic process. Such insults lead to the systemic inflammatory response syndrome (SIRS), which includes activation of leukocytes-alveolar macrophages and sequestered neutrophils-in the lung. Although systemic inflammatory response syndrome is a physiologic response to an insult, systemic leukocyte activation, if excessive, can lead to end organ injury, such as ALI. Excessive recruitment of leukocytes is critical to the pathogenesis of ALI, and the magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ALI. Leukocyte recruitment is a well orchestrated process that depends on the function of chemokines and their receptors. Understanding the mechanisms that contribute to leukocyte recruitment in ALI may ultimately lead to the development of effective therapeutic strategies.
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              Innate cell communication kick-starts pathogen-specific immunity.

              Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of 'trained' innate cells that facilitate the rapid elimination of homologous or heterologous infections.
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                Author and article information

                Contributors
                palomaduarte@gmail.com
                fabi.lauretti.bio@gmail.com
                maiara_caldas@hotmail.com
                swiany@gmail.com
                ambart.covarrubias@uss.cl
                mdf171717@gmail.com
                eneas.carvalho@butantan.gov.br
                paulo.ho@butantan.gov.br
                rdacosta@dndi.org
                elizabeth.martins@butantan.gov.br
                josefa.silva@butantan.gov.br
                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central (London )
                1471-2180
                7 January 2019
                7 January 2019
                2019
                : 19
                : 4
                Affiliations
                [1 ]ISNI 0000 0001 1702 8585, GRID grid.418514.d, Laboratório de Bacteriologia, , Instituto Butantan, ; São Paulo, Brazil
                [2 ]ISNI 0000 0000 9688 4664, GRID grid.472872.c, Fundação Ezequiel Dias, ; Belo Horizonte, Brazil
                [3 ]GRID grid.442215.4, School of Medical Technology, Faculty of Health Sciences, , University San Sebastian, ; Concepción, Chile
                [4 ]Instituto Pasteur, São Paulo, Brazil
                [5 ]ISNI 0000 0001 1702 8585, GRID grid.418514.d, Seção de Vacinas Aeróbicas, , Instituto Butantan, ; São Paulo, Brazil
                [6 ]ISNI 0000 0001 1702 8585, GRID grid.418514.d, Laboratório de desenvolvimento de processos, , Instituto Butantan, ; São Paulo, Brazil
                [7 ]GRID grid.428391.5, Present address: Global Antibiotics Research and Development Partnership (GARDP), , Drugs for Neglected Diseases initiative (DNDi), ; Chemin Louis-Dunant 15, 1202 Geneva, Switzerland
                Author information
                http://orcid.org/0000-0003-3884-7111
                Article
                1371
                10.1186/s12866-018-1371-9
                6323685
                30616505
                b61132b1-c7a9-4ef8-b11f-a663e8f80a64
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 October 2018
                : 10 December 2018
                Funding
                Funded by: FAPESP
                Award ID: 2013/16451-1
                Funded by: CNPq
                Award ID: 473035/2013-8
                Award ID: None
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100005942, Fundação Butantan;
                Award ID: None
                Award ID: None
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Microbiology & Virology
                phagocytosis,leptospira,chemokines,ccl2/mcp-1,c3h/hej,c3h/hepas
                Microbiology & Virology
                phagocytosis, leptospira, chemokines, ccl2/mcp-1, c3h/hej, c3h/hepas

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