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 Δ 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. γδ + T cells appear able to compensate for the absence of αβ + 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.

Vaccine Candidate Brucella melitensis 16M ΔvjbR Is Safe in a Pregnant Sheep Model and Confers Protection

“…As expected, 5 of 6 (83.3%) nonpregnant ewes previously challenged with 16M did not have recoverable organisms from the tissues evaluated because the primary infection provided protection against a secondary infection (7, 27, 28). It is well documented that an initial infection with a pathogen can provide protection against a secondary infection with the same or similar pathogens due to a convergence of acquired immune factors that stimulate a rapid response to infection (27,28). Even though 16M⌬vjbR is attenuated compared with Rev.…”

Dynamic Changes of Th1 Cytokines and the Clinical Significance of the IFN-γ/TNF-α Ratio in Acute Brucellosis

“…Once a patient becomes infected, the bacteria disturb the immune system of the host, activating several types of immune cells, including T and B lymphocytes, natural killer (NK) cells, macrophages, and neutrophils, as well as proinflammatory cytokines that can contribute to the destruction of the bacteria [4–6]. Directly after infection, naïve CD4 + T cells activate and differentiate into different subsets of functional T cells, such as IFN- γ -secreting T-helper type 1 (Th1) cells, transforming growth factor-beta 1- (TGF- β 1-) secreting T regulatory cells (Tregs), and interleukin- (IL-) 4-secreting Th2 cells [7–9]. In response to the foreign antigen, Th1 cells produce gamma-interferon (IFN- γ ), various interleukin (IL), and tumor necrosis factors (TNF).…”

Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

“… Antibody-Dependent Enhancement (where enhanced virus entry and replication in a number of cell types is enabled by antibodies) [ [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] ]; Intrinsic Antibody-Dependent Enhancement (where non-neutralizing antibodies raised by natural infection with one virus may enhance infection with a different virus) [ [55] , [56] , [57] , [58] , [59] , [60] , [61] ]; Immune Enhancement (enhancement of secondary infections via immune interactions) [ [62] , [63] , [64] , [65] ]; Cross-reactivity (an antibody raised against one specific antigen has a competing high affinity toward a different antigen.) [ 66 , 67 ] Cross-Infection Enhancement (infection enhancement of one virus by antibodies from another virus) [ 68 , 69 ] Vaccine-associated Virus Interference (where vaccinated individuals may be at increased risk for other respiratory viruses because they do not receive the non-specific immunity associated with natural infection) [ [70] , [71] , [72] , [73] , [74] , [75] ]; Vaccine-Associated Imprinting Reduction (where vaccinations could also reduce the benefits of ‘imprinting’, a protection conferred upon children who experienced infection at an early age) [ 76 , 77 ]; Non-Specific Vaccine Effects on Immune System (where previous infections can alter an individual's susceptibility to unrelated diseases) [ 78 , 79 ]; Impact of Infection Route on Immune System (where immune protection can be influenced by the route of exposure/delivery) [ [80] , [81] , [82] ]; ...…”