Innate resistance to infection by intracellular bacterial pathogens differs in mice selected for maximal or minimal acute inflammatory response

Abstract

The intensity of nonspecific immune reaction and the host resistance to facultative intracel-lular pathogens are found to be associated in lines of mice selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reactivity. AIRmax are more resistant than AIRmin mice to Salmonella typhimurium and Listeria monocytogenes infection, the differences between lines in LD 50 being G 1000 and 100 times, respectively. This difference was shown to be related to the initial bacterial containment at the infectious focus, and to the control of bacterial multiplication in the spleen during the 1st week after s. c. inoculation of the bacteria. Specific immune responses were not deeply affected by the selective process: antibody production and delayed-type hypersensitivity were both of similar intensity in AIRmax and AIRmin mice. The differential susceptibility to infection seems independent of the Nramp-1 locus polymorphism; therefore, these two lines represent a powerful model for investigating the role of other genetic loci regulating the nonspecific immunity effectors in the course of infectious diseases.

Periodontitis and arthritis interaction in mice involves a shared hyper-inflammatory genotype and functional immunological interferences

“…Indeed, RA can increase the incidence and severity of PD (independently or only partially dependent) of oral hygiene status or modifying factors. [4][5][6][7]15,16,35 Accordingly, our results show that PIA increase the severity of ePD in AIRmax mice strain, whereas in AIRmin strain (resistant to PIA development), [25][26][27][28] the severity of ePD was not altered by pristane injection, showing that the development of PIA, and not the pristane injection, is involved in the modulation of ePD severity. Similarly, adjuvant-induced arthritis in rats also results in signs of periodontal destruction.…”

“…15,16 Experimental studies reinforce the noncausal shared genetic susceptibility hypothesis as mouse lines phenotype selected for the acute inflammatory reactivity maximum (AIRmax) or minimal (AIRmin) share the susceptibility or resistance phenotype to both chronic models of pristane-induced arthritis (PIA) and Actinobacillus actinomycetemcomitansinduced PD. [24][25][26][27][28] AIRmax and AIRmin mice were developed through bidirectional genetic selection, starting from a highly polymorphic population (F0) derived from the intercrossing of eight inbred mouse strains (A, DBA2, P, SWR, CBA, SJL, BALB/c, and C57BL/6), and the progressive divergence of the AIRmax and AIRmin lines during successive generations of selective breeding reached 20-and 2.5-fold differences in leukocyte infiltration and exudated protein concentrations, respectively. 27 These differences resulted from the accumulation of alleles endowed with opposite and additive effects on the inflammatory response.…”

Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

“…As mentioned previously, the Slc11a1 gene region could be one of these QTL. 24 The identification of the loci influencing RA in animal models is important for parallel genetic studies in humans. In mice, several loci were identified in different models of experimental arthritis.…”

“…Most of the AIRmax animals carry the R allele, while 90% of AIRmin animals carry the S allele. 24 This differential allele segregation suggests that this chromosomal region harbors an acute inflammation modifier QTL. The Slc11a1 gene is the obvious candidate, mainly owing to its role in macrophage activation, 17 in addition to Il8rb, which is located in the same region (mouse genome database, www.informatics.jax.gov).…”

“…Our results suggest that these frequency changes were the result of selection processes, and implicate this gene, or other closely linked genes, in the control of the acute inflammatory reaction intensity. 24 In order to study the interaction of the Slc11a1 alleles with the acute inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax RR , AIRmax…”