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Route of Infection Strongly Impacts the Host-Pathogen Relationship.

ABSTRACT: Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of Brucella melitensis infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated that the route of infection strongly impacts all of these parameters. Following i.p. and i.n. infection, most infected cells observed in the spleen or lung were F4/80⁺ myeloid cells. In striking contrast, infected Ly6G⁺ neutrophils and CD140a⁺ fibroblasts were also observed in the skin after i.d. infection. The virB operon encoding for the type IV secretion system is considered essential to deflecting vacuolar trafficking in phagocytic cells and allows Brucella to multiply and persist. Unexpectedly, the ?virB Brucella strain, which does not persist in the lung after i.n. infection, persists longer in skin tissues than the wild strain after i.d. infection. While the CD4⁺ T cell-mediated Th1 response is indispensable to controlling the Brucella challenge in the i.p. model, it is dispensable for the control of Brucella in the i.d. and i.n. models. Similarly, B cells are indispensable in the i.p. and i.d. models but dispensable in the i.n. model. ??⁺ T cells appear able to compensate for the absence of ??⁺ T cells in the i.d. model but not in the other models. Taken together, our results demonstrate the crucial importance of the route of infection for the host pathogen relationship.

SUBMITTER: Demars A

PROVIDER: S-EPMC6637429 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Route of Infection Strongly Impacts the Host-Pathogen Relationship.

Demars Aurore A Lison Aurore A Machelart Arnaud A Van Vyve Margaux M Potemberg Georges G Vanderwinden Jean-Marie JM De Bolle Xavier X Letesson Jean-Jacques JJ Muraille Eric E

Frontiers in immunology 20190711

Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of <i>Brucella melitensis</i> infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated ...[more]

PMID: 31354728

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Project description:Major contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host-pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic characterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of the prevalence of sympatric and allopatric TB in relation to patients' age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the Euro-American lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants.

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Route of Infection Strongly Impacts the Host-Pathogen Relationship.

Publications

Route of Infection Strongly Impacts the Host-Pathogen Relationship.

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