Characterization of the bovine innate immune response to intramammary infection with Klebsiella pneumoniae

Gram-negative bacteria are responsible for almost one-half of the clinical cases of mastitis that occur annually. Of those gram-negative bacteria that induce mastitis, Klebsiella pneumoniae remains one of the most prevalent. Detection of infectious pathogens and the induction of a proinflammatory response are critical components of host innate immunity. The objective of the current study was to characterize several elements of the bovine innate immune response to intramammary infection with Klebsiella pneumoniae. The inflammatory cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS)-binding protein (LBP), 2 proteins that contribute to host recognition of gram-negative bacteria, were studied. The contralateral quarters of 7 late-lactating Holstein cows were challenged with either saline or K. pneumoniae, and milk and blood samples were collected. Initial increases in the chemoattractants C5a and IL-8, as well as TNF-alpha, were evident in infected quarters within 16 h of challenge and were temporally coincident with increases in milk somatic cells. Augmented levels of TNF-alpha and IL-8 were observed in infected quarters until >48 h postchallenge, respectively. Elevated levels of IL-12, IFN-gamma, and the antiinflammatory cytokine, IL-10, which were first detected between 12 and 20 h postinfection, persisted in infected quarters throughout the study (>96 h). Initial increases in milk LBP and sCD14 were detected 16 and 20 h, respectively, after challenge. Together, these data demonstrate that intramammary infection with K. pneumoniae elicits a host response characterized by the induction of proinflammatory cytokines and elevation of accessory molecules involved in LPS recognition.     

Dissociating context and space within the hippocampus: Effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning.

Rats with complete excitotoxic hippocampal lesions or selective damage to the dorsal or ventral hippocampus were compared with controls on measures of contextually conditioned freezing in a signaled shock procedure and on a spatial water-maze task. Complete and ventral lesions produced equivalent, significant anterograde deficits in conditioned freezing relative to both dorsal lesions and controls. Complete hippocampal lesions impaired water-maze performance; in contrast, ventral lesions improved performance relative to the dorsal group, which was itself unexpectedly unimpaired relative to controls. Thus, the partial lesion effects seen in the 2 tasks never resembled each other. Anterograde impairments in contextual freezing and spatial learning do not share a common underlying neural basis; complete and ventral lesions may induce anterograde contextual freezing impairments by enhancing locomotor activity under conditions of mild stress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the entorhinal cortex in a process of attentional modulation: Evidence from a novel variant of an IDS/EDS procedure.

Novel behavioral assays were used to assess the role of the entorhinal cortex in modulating attention to components of stimulus compounds. In Stage 1, rats received discrimination training with compounds constructed from 3 dimensions (auditory, visual, and tactile); in each compound the combination of components from 2 dimensions (e.g., auditory and visual) were relevant to the solution of the discrimination, and the remaining dimension (e.g., tactile) was irrelevant. In Stage 2, rats received a different discrimination in which the relevant dimensions were either congruent (auditory and visual) or incongruent (auditory and tactile) with those that were relevant in Stage 1. Sham-operated rats acquired the congruent discrimination more rapidly than the incongruent discrimination—a finding indicative of a process of attentional modulation—whereas rats with excitotoxic lesions of the entorhinal cortex acquired both discriminations equally readily. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cumulative physiological events influence the inflammatory response of the bovine udder to Escherichia coli infections during the transition period

A high proportion of intramammary coliform infections present at parturition develop disease characterized by severe inflammatory signs and sepsis during the first 60 to 70 d of lactation. In the lactating bovine mammary gland, the innate immune system plays a critical role in determining the outcome of these infections. Since the beginning of the 1990s, research has increased significantly on bovine mammary innate defense mechanisms in connection with the pathogenesis of coliform mastitis. Neutrophils are key effector cells of the innate immune response to intramammary infection, and their function is influenced by many physiological events that occur during the transition period. Opportunistic infections occur when the integrity of the host immune system is compromised by physical and physiological conditions that make the host more susceptible. The innate immune system of many periparturient cows is immunocompromised. It is unlikely that periparturient immunosuppression is the result of a single physiological factor; more likely, several entities act in concert, with profound effects on the function of many organ systems of the periparturient dairy cow. Their defense system is unable to modulate the complex network of innate immune responses, leading to incomplete resolution of the pathogen and the inflammatory reaction. During the last 30 yr, most efforts have been focused on neutrophil diapedesis, phagocytosis, and bacterial killing. How these functions modulate the clinical outcome of coliform mastitis, and how they can be influenced by hormones and metabolism has been the subject of intensive research and is the focus of this review. The afferent (sensing) arm of innate immunity, which enables host recognition of a diverse array of pathogens, is the subject of intense research interest and may contribute to the variable inflammatory response to intramammary infections during different stages of lactation. The development of novel interventions that modulate the inflammatory response or contribute to the elimination of the pathogen or both may offer therapeutic promise in the treatment of mastitis in periparturient cows.     

Increased levels of LPS-binding protein in bovine blood and milk following bacterial lipopolysaccharide challenge

Several species of gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, and various species of Enterobacter, are common mastitis pathogens. All of these bacteria are characterized by the presence of endotoxin or lipopolysaccharide (LPS) in their outer membrane. The bovine mammary gland is highly sensitive to LPS, and LPS has been implicated, in part, in the pathogenesis of gram-negative mastitis. Recognition of LPS is a key event in the innate immune response to gram-negative infection and is mediated by the accessory molecules CD14 and LPS-binding protein (LBP). The objective of the current study was to determine whether LBP levels increased in the blood and mammary gland following LPS challenge. The left and right quarters of five midlactating Holstein cows were challenged with either saline or LPS (100 microg), respectively, and milk and blood samples collected. Basal levels of plasma and milk LBP were 38 and 6 microg/ml, respectively. Plasma LBP levels increased as early as 8 h post-LPS challenge and reached maximal levels of 138 microg/ ml by 24 h. Analysis of whey samples derived from LPS-treated quarters revealed an increase in milk LBP by 12 h. Similar to plasma, maximal levels of milk LBP (34 microg/ml) were detected 24 h following the initial LPS challenge. Increments in milk LBP levels paralleled a rise in soluble CD14 (sCD14) levels and initial rises in the levels of these proteins were temporally coincident with maximal neutrophil recruitment to the inflamed gland. Because LBP and sCD14 are known to enhance LPS-induced host cell activation and to facilitate detoxification of LPS, these data are consistent with a role for these molecules in mediating mammary gland responses to LPS.     

Attentional bias to brief threat-related faces revealed by saccadic eye movements.

According to theories of emotion and attention, we are predisposed to orient rapidly toward threat. However, previous examination of attentional cueing by threat showed no enhanced capture at brief durations, a finding that may be related to the sensitivity of the manual response measure used. Here we investigated the time course of orienting attention toward fearful faces in the exogenous cueing task. Cue duration (20 ms or 100 ms) and response mode (saccadic or manual) were manipulated. In the saccade mode, both enhanced attentional capture and impaired disengagement from fearful faces were evident and limited to 20 ms, suggesting that saccadic cueing effects emerge rapidly and are short lived. In the manual mode, fearful faces impacted only upon the disengagement component of attention at 100 ms, suggesting that manual cueing effects emerge over longer periods of time. Importantly, saccades could reveal threat biases at brief cue durations consistent with current theories of emotion and attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze.

[Correction Notice: An erratum for this article was reported in Vol 117(5) of Behavioral Neuroscience (see record 2007-16848-001). The definitions "Present = intramaze landmark present during Stage 2" and "Absent = intramaze landmark absent during Stage 2" appear incorrectly in the caption to Figure 3. These terms and definitions should appear in the caption to Figure 4.] This study with rats examined the effects of excitotoxic lesions to the entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a disruption to the use of extramaze cues, but not intramaze cues, whereas EC lesions had no effect on the use of these cues when they were encountered for the fast time. However, prior navigation training in which 1 type of cue was relevant disrupted navigation with the other type in rats with EC lesions. Results show that the EC contributes to the processing of spatial information, but that this contribution is most apparent when there is a conflict between 2 sources of navigational cues in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Mesocortical Dopamine Projection to Anterior Cingulate Cortex Plays No Role in Guiding Effort-Related Decisions.

Both mesolimbic dopamine (DA) and the anterior cingulate cortex (ACC) have been implicated in enabling animals to expend effort to obtain greater reward. To investigate the role of the DA pathway to ACC in working for reward, the authors tested rats on a cost-benefit T-maze paradigm in which they could either climb a barrier to obtain large reward in 1 arm (high reward [HR]) or select the low-effort alternative containing less reward (low reward [LR]). Surprisingly, ACC DA depletions had no effect on choice performance. Manipulations of barrier and reward sizes demonstrated that lesioned rats were as sensitive to the costs and benefits of the alternatives as controls. These results imply that the DA projection to ACC is not involved in guiding effort-related decisions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of function within the hippocampus: A comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions.

Rats with complete cytotoxic hippocampal lesions exhibited spatial memory impairments in both the water maze and elevated T maze. They were hyperactive in photocell cages; swam faster in the water maze; and were less efficient on a nonspatial, differential reinforcement of low rates (DRL) task. Performance on both spatial tasks was also impaired by selective dorsal but not ventral lesions; swim speed was increased by ventral but not dorsal lesions. Both partial lesions caused a comparable reduction in DRL efficiency, although these effects were smaller than those of complete lesions. Neither partial lesion induced hyperactivity when rats were tested in photocell cages, although both complete and ventral lesion groups showed increased activity after footshock in other studies (Richmond et al., see record 1999-01985-006). These results demonstrate possible functional dissociations along the septotemporal axis of the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)