Stress-induced differences in primary and secondary resistance against bacterial sepsis corresponds with diverse corticotropin releasing hormone receptor expression by pulmonary CD11c+ MHC II+ and CD11c− MHC II+ APCs

Abstract

Stress responses have been associated with altered immunity and depending upon the type of stressor, can have diverse effects on disease outcomes. As the first line of defense against potential pathogens, alterations in cellular immune responses along the respiratory tract can have a significant impact on the manifestation of local and systemic disease. Utilizing a murine model of respiratory pneumonia, the current study investigated the effects of restraint stress on the induction of primary and secondary immunity along the respiratory tract, influencing host susceptibility. Female CD-1 mice were subjected to three hours of restraint stress over a period of four days followed by primary and secondary Streptococcus pneumoniae infection via intranasal route. Stress exposure led to increased retention of bacterial carriage in the lungs, enhanced polymorphonuclear cells and a preferential decrease in pulmonary CD11c(+) MHC II(+) cells resulting in delayed lethality during primary infection but significant impairment of acquired immune protection after secondary infection. We also provide evidence to support a role for lung-associated corticotropin releasing hormone regulation through peripheral CRH and diverse CRH receptor expression by MHC II(+) antigen presenting cells (APCs). We conclude that repeated restraint stress has distinct influences on immune cell populations that appear to be important in the generation of innate and adaptive immune responses along the respiratory tract with the potential to influence local and systemic protection against disease pathogenesis.

Catecholamine norepinephrine diminishes lung epithelial cell adhesion of Streptococcus pneumoniae by binding iron

“…NE attenuates overall disease progression in experimental stress models of pneumococcal pneumonia (Gonzales et al, 2008), a finding that is in contrast to results with other pathogens where disease is enhanced (Bansal et al, 2007;Cogan et al, 2007;Hegde et al, 2009;Scheckelhoff et al, 2007;Vlisidou et al, 2004). In this study, we identified that at least one interface between NE and the bacterial-host interaction is at the initial stage of pneumococcal adherence to epithelial surfaces.…”

“…The interaction of NE and pneumococcal pneumonia has been investigated using an immobilization stress model that increases plasma NE levels (Kvetnansky, 2004). In contrast to other infections, increased NE was associated with less pneumococcal invasion from lung to blood and lethality was delayed (Gonzales et al, 2008). This suggests that, unlike findings with many infections, the interaction of NE and pneumococci leads to less invasion and improves outcome.…”

Effects of restraint stress on NALT structure and nasal IgA levels

“…Although there are no previous reports of stress on these parameters of the NALT, other studies have found a reduction in the size of primary lymphoid organs (e.g., the thymus) and secondary nodes and spleen (e.g., the mesenteric lymphoid) [46][47][48][49][50]. Therefore, it is possible that the NALT of Balb/c mice is more resistant to the effects of stress (e.g., apoptosis) than other lymphoid organs, which are modified significantly with short-term and long-term restraint stress protocols [51,52].…”

Contaminated Water Delivery as a Simple and Effective Method of Experimental Salmonella Infection

“…However, given the stress of the gavage procedure and the possibility for esophageal tearing, it is important that this assumption is actually tested [33, 35]. Stress has a number of physiological effects in mice that could potentially impact microbiological and immunological studies [38, 41, 44]. Further, the possibility that a pathogen is introduced to the bloodstream or lung during the gavage procedure could also impact the kinetics of infection and subsequent immune response [57, 60].…”

“…However, a major drawback to this method is that the gavage needle has the potential to damage the esophageal lining, raising some concern that bacteria could use experimentally-induced abrasions to access the host via an unnatural route [8, 32–34]. In addition, the restraint and manipulation required for effective oral gavage dosing induces significant stress in experimental animals [33, 35, 36], which could potentially impact the immune response [37–40] and/or susceptibility to infection [41–44]. Taken together, although oral gavage is an effective means of oral infection, the procedure itself has the potential to affect the route of bacterial entry and the subsequent host response.…”