Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity
Francisella tularensis is a Select Agent that causes the severe disease tularemia in humans and many animal species. The bacterium demonstrates rapid intracellular replication, however, macrophages can control its replication if primed and activation with IFN-γ is known to be essential, although alo...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-12-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2020.594063/full |
| _version_ | 1819315518137434112 |
|---|---|
| author | Nasibeh Mohammadi Helena Lindgren Igor Golovliov Kjell Eneslätt Masahiro Yamamoto Amandine Martin Thomas Henry Anders Sjöstedt |
| author_facet | Nasibeh Mohammadi Helena Lindgren Igor Golovliov Kjell Eneslätt Masahiro Yamamoto Amandine Martin Thomas Henry Anders Sjöstedt |
| author_sort | Nasibeh Mohammadi |
| collection | DOAJ |
| description | Francisella tularensis is a Select Agent that causes the severe disease tularemia in humans and many animal species. The bacterium demonstrates rapid intracellular replication, however, macrophages can control its replication if primed and activation with IFN-γ is known to be essential, although alone not sufficient, to mediate such control. To further investigate the mechanisms that control intracellular F. tularensis replication, an in vitro co-culture system was utilized containing splenocytes obtained from naïve or immunized C57BL/6 mice as effectors and infected bone marrow-derived wild-type or chromosome-3-deficient guanylate-binding protein (GBP)-deficient macrophages. Cells were infected either with the F. tularensis live vaccine strain (LVS), the highly virulent SCHU S4 strain, or the surrogate for F. tularensis, F. novicida. Regardless of strain, significant control of the bacterial replication was observed in co-cultures with wild-type macrophages and immune splenocytes, but not in cultures with immune splenocytes and GBPchr3-deficient macrophages. Supernatants demonstrated very distinct, infectious agent-dependent patterns of 23 cytokines, whereas the cytokine patterns were only marginally affected by the presence or absence of GBPs. Levels of a majority of cytokines were inversely correlated to the degree of control of the SCHU S4 and LVS infections, but this was not the case for the F. novicida infection. Collectively, the co-culture assay based on immune mouse-derived splenocytes identified a dominant role of GBPs for the control of intracellular replication of various F. tularensis strains, regardless of their virulence, whereas the cytokine patterns markedly were dependent on the infectious agents, but less so on GBPs. |
| first_indexed | 2024-12-24T10:01:23Z |
| format | Article |
| id | doaj.art-5d18e86b2ea24bdb81748e89f88e4dd2 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-24T10:01:23Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-5d18e86b2ea24bdb81748e89f88e4dd22022-12-21T17:01:01ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-12-011010.3389/fcimb.2020.594063594063Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive ImmunityNasibeh Mohammadi0Helena Lindgren1Igor Golovliov2Kjell Eneslätt3Masahiro Yamamoto4Amandine Martin5Thomas Henry6Anders Sjöstedt7Department of Clinical Microbiology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Clinical Microbiology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Clinical Microbiology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Clinical Microbiology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka, JapanCIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Univ Lyon, Lyon, FranceCIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Univ Lyon, Lyon, FranceDepartment of Clinical Microbiology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenFrancisella tularensis is a Select Agent that causes the severe disease tularemia in humans and many animal species. The bacterium demonstrates rapid intracellular replication, however, macrophages can control its replication if primed and activation with IFN-γ is known to be essential, although alone not sufficient, to mediate such control. To further investigate the mechanisms that control intracellular F. tularensis replication, an in vitro co-culture system was utilized containing splenocytes obtained from naïve or immunized C57BL/6 mice as effectors and infected bone marrow-derived wild-type or chromosome-3-deficient guanylate-binding protein (GBP)-deficient macrophages. Cells were infected either with the F. tularensis live vaccine strain (LVS), the highly virulent SCHU S4 strain, or the surrogate for F. tularensis, F. novicida. Regardless of strain, significant control of the bacterial replication was observed in co-cultures with wild-type macrophages and immune splenocytes, but not in cultures with immune splenocytes and GBPchr3-deficient macrophages. Supernatants demonstrated very distinct, infectious agent-dependent patterns of 23 cytokines, whereas the cytokine patterns were only marginally affected by the presence or absence of GBPs. Levels of a majority of cytokines were inversely correlated to the degree of control of the SCHU S4 and LVS infections, but this was not the case for the F. novicida infection. Collectively, the co-culture assay based on immune mouse-derived splenocytes identified a dominant role of GBPs for the control of intracellular replication of various F. tularensis strains, regardless of their virulence, whereas the cytokine patterns markedly were dependent on the infectious agents, but less so on GBPs.https://www.frontiersin.org/articles/10.3389/fcimb.2020.594063/fullFrancisella tularensisguanylate-binding proteinsmouse co-culture modelcytokine patternscorrelates of protection |
| spellingShingle | Nasibeh Mohammadi Helena Lindgren Igor Golovliov Kjell Eneslätt Masahiro Yamamoto Amandine Martin Thomas Henry Anders Sjöstedt Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity Frontiers in Cellular and Infection Microbiology Francisella tularensis guanylate-binding proteins mouse co-culture model cytokine patterns correlates of protection |
| title | Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity |
| title_full | Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity |
| title_fullStr | Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity |
| title_full_unstemmed | Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity |
| title_short | Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity |
| title_sort | guanylate binding proteins are critical for effective control of francisella tularensis strains in a mouse co culture system of adaptive immunity |
| topic | Francisella tularensis guanylate-binding proteins mouse co-culture model cytokine patterns correlates of protection |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2020.594063/full |
| work_keys_str_mv | AT nasibehmohammadi guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT helenalindgren guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT igorgolovliov guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT kjelleneslatt guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT masahiroyamamoto guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT amandinemartin guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT thomashenry guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity AT anderssjostedt guanylatebindingproteinsarecriticalforeffectivecontroloffrancisellatularensisstrainsinamousecoculturesystemofadaptiveimmunity |