The Immunology of Mammary Gland of Dairy Ruminants between Healthy and Inflammatory Conditions

Table 4

BMG immune response towards different mastitis-causative bacteria.

Staph. aureus	(i) Both SCC and leukocyte count increase (mainly PMNs), but leukocytes are not in a highly activated state [17, 86].; (ii) The CD8+ lymphocytes are preferentially recruited over CD4+ lymphocytes [78, 86].; (iii) Increase in the proportion of the B-lymphocytes in the total lymphocyte population, revealing development of humoral responses. No change was observed in the T-lymphocyte subset [86].; (iv) Variable increases in IL-1, IL-1, IL-6, IL-12, TNF-, IFN-, GM-CSF, GRO, and soluble CD14 [86, 114, 165, 329, 350].; (v) Depression of IL-2 and IL-4 levels [86, 350].; (vi) Chemoattractant IL-8 showed an undetectable change [165, 239] or slight increase [114, 329]. A lower level of C5a was observed [239].; (vii) Like IL-8, the anti-inflammatory cytokine IL-10 may exhibit an increase [86] or an undetectable increase [114].; (viii) The gene encoding proinflammatory cytokine IL-17A shows an increase in tissues of infected MG [17].; (ix) TGF- showed no marked release [114]; meanwhile, a study by [135] showed increased TGF- expression in MG. On the other hand, expression of TGF- increased moderately in ductal tissue of MG and, on the contrary, moderately decreased in teat canal tissues [17].
Staph. epidermidis	In one comparative study by [354]: (i) Elevation of SCC, but lower than that observed with Staph. simulans.; (ii) Elevation of IL-1, IL-8, and TNF- levels in milk. Systematically there are no changes in these cytokines, although the cows showed mild to moderate signs of CM.
Staph. simulans	(i) Increased leukocyte counts in milk with severe infiltration of MG tissues with mononuclear cells and neutrophils [358].; (ii) Increased IL-1, TNF-, and IL-8 levels in milk, more than that elicited by Staph. epidermidis; however, the levels of these cytokines remained unchanged systemically [354].
S. uberis	(i) The early host response to S. uberis infection is characterized by a relatively slow but massive influx of PMNL in the infected MG [336, 337, 365]. The percentage of lymphocytes expressing CD44 increased 12 h PI [343].; (ii) Increased leukocyte counts in milk and decreased counts of circulating leukocytes [336, 337].; (iii) Robust increase of chemoattractants such as IL-8 and C5a [336, 337].; (iv) Marked elevation of IL-1 and TNF- proinflammatory cytokines, but the time of elevation differed among studies [209, 336, 337].; (v) Marked prolonged increase of IL-10, IL-12 [337], and IFN- [337, 367].; (vi) Elevation of sCD14 and LPS-BP, involved in host recognition of bacterial cell wall products; both of them remained elevated [337].; (vii) Investigation done to determine the most affected gene networks and pathways in MG tissue in response to an IMI with S. uberis has illustrated upregulation of several genes encoding IL6, TNF, IL8, IL10 and indicated that TNF had positive relationships with genes involved with immune system function (e.g., CD14, IL-8, IL-1, and TLR2) [362].; (viii) Likewise, in another study to evaluate the transcriptional changes that occur in the MG after the onset of clinical S. uberis mastitis, an increase in mRNA expression of immune-related genes, complement component 3, IL-8, IFN-, IL-10, IL-1, IL-6, TLR2, TNF-, LF, LPS-BP, and oxidative stress-related genes metallothionein 1A and superoxide dimutase 2, has been confirmed [196].
S. dysgalactiae	(i) Increased leukocyte counts in milk, mainly PMNs.; (ii) Increase of TLR4 expression and elevation of IL-1 and TNF- [361].
E. coli	(i) Rapid and intense increase in milk SCC [165] including increases in leukocyte counts and intense PMN recruitment to MG [127, 165, 239].; (ii) Marked elevation of proinflammatory, regulatory, and anti-inflammatory cytokines including IL-1, IL-6, IL-8, IL-10, IL-12, GM-CSF, IFN-, soluble CD14, GRO, C5a [127, 165, 307, 329], TGF-, TGF-1, and TGF-2 [311].; (iii) The level of TNF-α varied among studies, revealing undetectable values [307, 338, 339] or marked rises [114, 127, 165, 239, 329, 350, 377].
Serratia marcescens	Studies regarding S. marcescens were almost done in comparison to S. uberis [337, 343] showing the following.; (i) Systemic reaction peaking at 24 h PI in S. marcescens-infected cows and dropping thereafter, compared with 96 h PI in S. uberis-infected cows.; (ii) Increased leukocyte counts in milk while circulating leukocyte counts decreased.; (iii) Transient increase in chemoattractants such as IL-8 and C5a.; (iv) Transient increase in IL-1 and TNF- proinflammatory cytokine levels in milk. However, the peak of TNF- was more rapid and stronger compared to S. uberis. Likewise, IL-12 and IFN- were transiently increased.; (v) Small increase in the anti-inflammatory cytokine IL-10 at 18 h and then a return to the prechallenge level.; (vi) Transient increase of sCD14 and LPS-BP followed by a return to prechallenge levels.; (vii) Lymphocytes expressing either CD62L or CD11a showed a marked increase 12 h PI.
Klebsiella pneumoniae	One study [275] showed the following.; (i) Increased leukocyte counts in milk, mainly PMNs.; (ii) Marked rapid increase in IL-8 and C5a chemoattractants after challenge with pathogen and IL-1, TNF-, IL-12, and IFN- proinflammatory cytokines.; (iii) Marked increase in anti-inflammatory cytokine IL-10.; (iv) Increase of LPS-BP and sCD14.
Pseudomonas aeruginosa	One study [37] showed the following.; (i) Increase in SCC and leukocyte counts in milk for more than 3 weeks.; (ii) Early increased levels of IL-8, IL-10, IL-12, and TNF-. In contrast, IL-1, IFN-, TGF-, TGF-1, TGF-2, sCD14, LPS-BP, and C5a levels were elevated for sustained periods of >48 h.