Innate Mucosal Immune System Response of BALB/c vs C57BL/6 Mice to Injury in the Setting of Enteral and Parenteral Feeding

Abstract

Background Outbred mice exhibit increased airway and intestinal immunoglobulin A (IgA) following injury when fed normal chow, consistent with humans. Parenteral nutrition (PN) eliminates IgA increases at both sites. Inbred mice are needed for detailed immunological studies; however, specific strains have not been evaluated for this purpose. BALB/c and C57BL/6 are common inbred mouse strains, but demonstrate divergent immune responses to analogous stress. This study addressed which inbred mouse strain best replicates the outbred mouse and human immune response to injury. Methods Intravenously cannulated mice received Chow or PN for 5 days and then underwent sacrifice at 0 or 8-hours following controlled surgical injury (BALB/c: n=16-21/group; C57BL/6: n=12-15/group). Bronchoalveolar lavage (BAL) was analyzed by ELISA for IgA, TNF-α, IL-1β and IL-6 while small intestinal wash fluid (SIWF) was analyzed for IgA. Results No significant increase in BAL IgA occurred following injury in chow-or PN-fed BALB/c mice (Chow: p=0.1; PN: p=0.7) despite significant increases in BAL TNF-α and SIWF IgA (Chow: 264±28 vs. 548±37, p<0.0001; PN: 150±12 vs. 301±17, p<0.0001). Injury significantly increased mucosal IgA in chow-fed C57BL/6 mice (BAL: 149±33 vs. 342±87, p=0.01; SIWF: 236±28 vs. 335±32, p=0.006) and BAL cytokines. After injury, PN-fed C57BL/6 mice exhibited no difference in BAL IgA (p=0.9), BAL cytokines or SIWF IgA (p=0.1). Conclusions C57BL/6 mice exhibit similar airway responses to injury as outbred mice and humans, providing an appropriate model for studying mucosal responses to injury. The BALB/c mucosal immune system responds differently to injury and does not replicate the human injury response.

A Systematic Review of the Mechanisms Involved in Immune Checkpoint Inhibitors Cardiotoxicity and Challenges to Improve Clinical Safety

“…Supporting preclinical data have shown that co-inhibitory molecules are essential to prevent cardiac diseases ( Grabie et al, 2019 ) in which antibodies are related ( Nishimura et al, 2001 ; Okazaki et al, 2003 ). PD-1 deficiency causes dilated cardiomyopathy mediated by antibodies deposition on cardiac cells in mice with a Th2 bias response ( Nishimura et al, 2001 ; Okazaki et al, 2003 ), which are more prompt to develop a humoral response ( Busch et al, 2016 ). In contrast, mice with a Th1 bias (cellular immune response) developed atrial fibrillation ( Fu et al, 2013 ).…”

Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate airway hyperreactivity

“…This suggests that the PUFA-enriched diet induced a lung phenotype of innateairway hyperreactivity without other functional impairment typically associated with chronic inflammation or fibrosis. BALB/C and C57BL/6 were selected to assess if the innate airway hyperreactivity is independent of the genetic inflammatory haplotype 28 with Th1-and M1-dominant responses in C57BL/6, and Th2-and M2-dominant responses in BALB/c mice, respectively 29 . The effect was only evaluated in female mice.…”

Protection Elicited by Attenuated Live Yersinia pestis Vaccine Strains against Lethal Infection with Virulent Y. pestis

“…The CD-1 mice were less well protected than BALB/c inbred mice against aerosol challenge. These results might be attributable to differences in Th2 responses and/or possibly differences in mucosal humoral immunity between the two mouse strains [ 64 , 65 ]. It is also important to note that the CD-1 mice did inhale a greater number of aerosolized Y. pestis CFUs.…”