Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection
Background. To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings. Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or...
| Autores Principales: | BARQUERO-CALVO, ELIAS, Chaves-Olarte, Esteban, Weiss, David, Guzman-Verri, Caterina, Chacón-Díaz, Carlos, Rucavado, Alexandra, Moriyon, Ignacio, Moreno, Edgardo |
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PLOS ONE
2020
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http://hdl.handle.net/11056/18404 |
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RepoUNACR18404 |
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RepoUNACR184042020-10-22T09:01:55Z Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection BARQUERO-CALVO, ELIAS Chaves-Olarte, Esteban Weiss, David Guzman-Verri, Caterina Chacón-Díaz, Carlos Rucavado, Alexandra Moriyon, Ignacio Moreno, Edgardo BRUCELOSIS BRUCELLA BRUCELLA ABORTUS ENFERMEDADES INFECCIOSAS INFECTIOUS DISEASES INMUNOLOGÍA Background. To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings. Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-a-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance. We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections. Antecedentes. Para desentrañar la estrategia mediante la cual Brucella abortus establece infecciones crónicas, exploramos su temprana interacción con la inmunidad innata. Metodología/Hallazgos principales. Brucella no indujo respuestas proinflamatorias como lo demuestra la ausencia de reclutamiento de leucocitos, cambios humorales o de sangre celular en ratones. Brucella obstaculizó la función de los neutrófilos (PMN) y el agotamiento de los PMN no influyó en el curso de la infección. Brucella apenas indujo citoquinas roinflamatorias y consumía complemento, y era fuertemente resistente a los péptidos bactericidas, a los extractos de PMN y al suero. Brucella LPS (BrLPS), NH-polisacáridos, glucanos cíclicos, fragmentos de membrana externa o células bacterianas alteradas mostraron una baja actividad biológica en ratones y células. La falta de respuestas proinflamatorias no se debió a mecanismos inhibidores conspicuos mediados por la Brucella invasora o sus productos. Cuando se activó 24 h después de la infección, los macrófagos no mataron a Brucella, lo que indica que el nicho de replicación no era fusiogénico con lisosomas. La replicación intracelular de Brucella no interrumpió el ciclo celular ni causó citotoxicidad en las células knockout WT, TLR4 y TLR2. La inducción de TNF era dependiente de TLR4 y TLR2 para los vivos pero no para los muertos de B. abortus. Sin embargo, la replicación intracelular en las células knockout TLR4, TLR2 y TLR4/2 fue no se alteró y el curso de la infección y el desarrollo de la inmunidad anti-Brucella tras la inyección de BrLPS no se vio afectado en los ratones mutantes TLR4. Conclusión/Significado. Proponemos que Brucella ha desarrollado una estrategia de sigilo a través de la reducción, modificación y ocultación de PAMPs, asegurando de esta manera una baja actividad estimulatoria y toxicidad para las células. Esta estrategia permite a Brucella alcanzar su nicho de replicación antes de la activación de los mecanismos antimicrobianos por la inmunidad adaptativa. Este modelo es coherente con los perfiles clínicos observados en los seres humanos y en los huéspedes naturales al inicio de la infección y podría ser válido para los patógenos intracelulares filogenéticamente relacionados con Brucella que también causan infecciones de larga duración. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria 2020-10-21T21:09:02Z 2020-10-21T21:09:02Z 2007-07-18 http://purl.org/coar/resource_type/c_6501 http://hdl.handle.net/11056/18404 10.1371/journal.pone.0000631 eng Acceso abierto Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf PLOS ONE PLoS ONE 2(7): e631 |
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Universidad Nacional de Costa Rica |
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Repositorio UNA-Costa Rica |
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Inglés |
| topic |
BRUCELOSIS BRUCELLA BRUCELLA ABORTUS ENFERMEDADES INFECCIOSAS INFECTIOUS DISEASES INMUNOLOGÍA |
| spellingShingle |
BRUCELOSIS BRUCELLA BRUCELLA ABORTUS ENFERMEDADES INFECCIOSAS INFECTIOUS DISEASES INMUNOLOGÍA BARQUERO-CALVO, ELIAS Chaves-Olarte, Esteban Weiss, David Guzman-Verri, Caterina Chacón-Díaz, Carlos Rucavado, Alexandra Moriyon, Ignacio Moreno, Edgardo Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| description |
Background. To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings. Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous
inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-a-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was
not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance. We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections. |
| format |
Artículo |
| author |
BARQUERO-CALVO, ELIAS Chaves-Olarte, Esteban Weiss, David Guzman-Verri, Caterina Chacón-Díaz, Carlos Rucavado, Alexandra Moriyon, Ignacio Moreno, Edgardo |
| author_sort |
BARQUERO-CALVO, ELIAS |
| title |
Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| title_short |
Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| title_full |
Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| title_fullStr |
Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| title_full_unstemmed |
Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| title_sort |
brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection |
| publisher |
PLOS ONE |
| publishDate |
2020 |
| url |
http://hdl.handle.net/11056/18404 |
| _version_ |
1796097430419144704 |
| score |
12.231669 |