Whole Blood Transcriptome Analysis of Mycoplasma mycoides Subsp. mycoides-Infected Cattle Confirms Immunosuppression but Does Not Reflect Local Inflammation

Abstract

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm), is a severe respiratory disease of cattle responsible for major economic losses in sub-Saharan Africa. Disease control relies mainly on the use of empirically attenuated vaccines that provide limited protection. Thus, understanding the virulence mechanisms used by Mmm as well as the role of the host immune system in disease development, persistence, and control is a prerequisite for the development of new, rationally designed control strategies. The aim of this study was to assess the use of whole blood transcriptome analysis to study cattle-Mmm interactions, starting by the characterization of the bovine response to Mmm infection during the acute form of the disease. For that purpose, we compared the transcriptome profile of whole blood from six cattle, before challenge by contact with Mmm-infected animals and at the appearance of first clinical signs, using a bovine microarray. Functional analysis revealed that 680 annotated genes were differentially expressed, with an overwhelming majority of down-regulated genes characterizing an immunosuppression. The main bio-functions affected were “organismal survival”, “cellular development, morphology and functions” and “cell-to cell signaling and interactions”. These affected functions were consistent with the results of previous in vitro immunological studies. However, microarray and qPCR validation results did not highlight pro-inflammatory molecules (such as TNFα, TLR2, IL-12B and IL-6), whereas inflammation is one of the most characteristic traits of acute CBPP. This global gene expression pattern may be considered as the result, in blood, of the local pulmonary response and the systemic events occurring during acute CBPP. Nevertheless, to understand the immune events occurring during disease, detailed analyses on the different immune cell subpopulations, either in vivo, at the local site, or in vitro, will be required. Whole blood transcriptome analysis remains an interesting approach for the identification of bio-signatures correlating to recovery and protection, which should facilitate the evaluation and validation of novel vaccine formulations.

Comprehensive RNA-Seq Profiling to Evaluate the Sheep Mammary Gland Transcriptome in Response to Experimental Mycoplasma agalactiae Infection

“…mycoides subsp. mycoides [57]. This is of interest as inflammation is the most characteristic indication of CBPP.…”

“…The lack of regulation for these genes in the present study could also be due to the dilution of cytokine-producing immune cells in the mammary tissue. In addition, the migration of immune cells from the site of infection to local inflamed lymph nodes might also contribute to the observed results [57]. …”

Pro-Inflammatory Response of Bovine Polymorphonuclear Cells Induced by Mycoplasma mycoides subsp. mycoides

“…Acute-subacute CBPP pulmonary lesions from infected animals are characterized by a massive infiltration of inflammatory cells, with a relevant component represented by neutrophil granulocytes, together with the presence of high levels of some pro-inflammatory factors (TNFα, IL-1β, and IL-17A) (29). However, despite the clear inflammatory picture associated to CBPP lesions, transcriptomic analysis of blood samples collected from CBPP affected cattle showed that genes involved in inflammation mechanisms (as TNFα) were not upregulated during the infection (30). These findings highlight how the peripheral condition observed in blood does not necessarily reflect local inflammation, confirming the complexity of CBPP pathogenesis in which different cell types contribute to the disease development and progression.…”

Persistence in Livestock Mycoplasmas—a Key Role in Infection and Pathogenesis

“…Whole blood transcriptome profiling studies of M. suis-infected pigs and M. mycoides ssp. mycoides-infected cattle revealed a downregulation of the gene expression leading to a general immune suppression [45,46]. It must be considered that this global approach reflects the sum of all local and systemic inflammatory and immune relevant host responses during the acute phase of infection.…”